research article about nanomaterials

Materials Advances

Nanomaterials: a review of synthesis methods, properties, recent progress, and challenges.

* Corresponding authors

a Center of Research Excellence in Desalination & Water Treatment, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia E-mail: [email protected] , [email protected]

b Center for Environment and Water, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia

c Interdisciplinary Research Center for Membranes and Water Security, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia

d Department of Chemical & Biological Engineering, University of Alabama, Tuscaloosa, Alabama 35487-0203, USA E-mail: [email protected] , [email protected]

e Department of Mechanical Engineering, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia

Nanomaterials have emerged as an amazing class of materials that consists of a broad spectrum of examples with at least one dimension in the range of 1 to 100 nm. Exceptionally high surface areas can be achieved through the rational design of nanomaterials. Nanomaterials can be produced with outstanding magnetic, electrical, optical, mechanical, and catalytic properties that are substantially different from their bulk counterparts. The nanomaterial properties can be tuned as desired via precisely controlling the size, shape, synthesis conditions, and appropriate functionalization. This review discusses a brief history of nanomaterials and their use throughout history to trigger advances in nanotechnology development. In particular, we describe and define various terms relating to nanomaterials. Various nanomaterial synthesis methods, including top-down and bottom-up approaches, are discussed. The unique features of nanomaterials are highlighted throughout the review. This review describes advances in nanomaterials, specifically fullerenes, carbon nanotubes, graphene, carbon quantum dots, nanodiamonds, carbon nanohorns, nanoporous materials, core–shell nanoparticles, silicene, antimonene, MXenes, 2D MOF nanosheets, boron nitride nanosheets, layered double hydroxides, and metal-based nanomaterials. Finally, we conclude by discussing challenges and future perspectives relating to nanomaterials.

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N. Baig, I. Kammakakam and W. Falath, Mater. Adv. , 2021,  2 , 1821 DOI: 10.1039/D0MA00807A

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• Open access
• Published: 23 January 2023

The state of the art of nanomaterials and its applications in energy saving

• Hala. S. Hussein 1  

Bulletin of the National Research Centre volume  47 , Article number:  7 ( 2023 ) Cite this article

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Nanomaterials have emerged as a fascinating class of materials in high demand for a variety of practical applications. They are classified based on their composition, dimensions, or morphology. For the synthesis of nanomaterials, two approaches are used: top-down approaches and bottom-up approaches.

Main body of the abstract

Nanoscale materials and structures have the potential to be used in the production of newly developed devices with high efficiency, low cost, and low energy demand in a variety of applications. There are several contributions in renewable energy conversion and storage in the energy sector, such as solar photovoltaic systems, fuel cells, solar thermal systems, lithium-ion batteries, and lighting. Furthermore, nanofluid-based solar collectors are a new generation of solar collectors based on the use of nanotechnology. It has the potential to increase collector efficiency by up to 30%.

Short conclusion

Graphene and graphene derivatives are known as more efficient energy-saving materials, with the ability to maximize heat transfer efficiency and save up to 30% of energy in water desalination. Silver nanoparticles (Ag NPs) are a powerful antibacterial material that can kill a wide variety of microorganisms. They are commonly used in water treatment and are incorporated into polyethersulfone (PES) microfiltration membranes. The use of an Ag-PES membrane improved the antibiofouling performance of PES membranes. From the industrial application of nanotechnology, applications of TiO 2 -based nanocoatings that can be used as dust-repellent coatings for solar panels improve their efficiency and reduce the amount of required maintenance. Furthermore, the nanoscale dimension of these particles facilitates their movement in various body parts, resulting in serious diseases such as cancer and organ damage. As a result, it is suggested to focus in our incoming research on the disposal of nanomaterial waste and their safe application.

• Nanomaterials

Generally, any powdered materials with particle diameter ranged from 1 to 100 nm are categorized as nanosized materials (Manaktala and Singh 2016 ; Changseok et al. 2013 ). Accordingly, the nanomaterials have received much interest because of their high efficiency in many applications, such as smart coating devices (e.g., thermochromic, photochromic, and electrochromic devices), solar energy systems, and sensing. Also, they also improve efficiency and lower prices in a variety of fields, including solar photovoltaic systems, hydrogen production, and fuel cells. (Mageswari et al. 2016 ; Baig et al. 2021 ). Moreover, nanomaterials demonstrated unique chemical, physical, and biological properties that they can be applied in different fields.

Classification of nanomaterials

There are three types of nanomaterials based on their composition, including inorganic-, organic-, and carbon-based materials as shown in Table 1 . Owing to unique size, nanomaterials exhibited higher reactivity, high sensitivity, large surface area, and strength.

Additionally, the nanoparticles can be categorized according to their dimensions (Jeevanandam et al. 2018 ; Buzea et al. 2016 ) exhibiting one or more dimensions within the nanoscale. The nanomaterials made from different materials demonstrate one nanoscale dimension such as surface coating attached on a substrate. By contrast, nanomaterials with two dimensions are usually nanoparticles applied on a substrate, nanoporous alumina wires or tubes, and nanoporous thin films. Three-dimensional nanomaterials can be exhibited a small nanostructure of a substrate or nanoporous membranes on a substrate. Nanomaterials can also be classified based on their morphology, such as nanocubes and nanowires. Finally, they can be graded according to their uniformity and agglomeration as represented in Fig.  1

Classification of nanostructured materials based on their morphology, dimensionality, composition, uniformity, and agglomeration state (Baig et al. 2021 )

Synthesis of nanomaterials

As stated by Singh et al. 2020 , top-down and bottom-up methods are the main approaches used for synthesizing nanomaterials (Fig.  2 ). For top-down strategy, coarse materials are disintegrated into nanostructured particles using laser ablation, mechanical milling, etching, electroexplosion, and sputtering. Meanwhile, bottom-up strategy includes spinning, vapor deposition, and sol–gel process.

The synthesis of nanomaterials via top-down and bottom-up approaches (Baig et al. 2021 )

Top-down methods

Mechanical milling.

This method is considered as a cost-efficient approach, in which the bulky materials transformed into nanosized ones. A blend of different nanophases as well as nanocomposites, such as copper-based nanoalloys and aluminum nickel magnesium, can be effectively prepared using this method (Sharma et al. 2021 ) .

Electrospinning

It is regarded as one of the simplest top-down methods for synthesizing nano-based materials. This method is usually applied for synthesizing nanofiber-based polymers such as polyurethane nanofibrous membranes (Xiao et al. 2022 ).

Sputtering is a technique for producing nanoscale materials by blasting solid objects with high-energy particles delivered by plasma or gas. It is regarded as a viable technology for creating nanoscale thin film. Sputtering is a process in which intense gaseous ions bombard the target surface, causing the physical discharge of small-sized atom clusters based on the energy of the incident gaseous ion (Chodun et al. 2022 ).

Laser ablation

The process of laser ablation synthesis entails the formation of nanoparticles by shattering the target material with a powerful laser beam. In this method, high-energy laser irradiation caused a vaporization of the precursor or source material to yield nanosized materials. Owing to there is no need for chemical or stabilizing agent, laser ablation approach is categorized as a green method for synthesizing noble nanosized metals.

Bottom-up methods

Chemical vapor deposition (cvd).

The chemical vapor deposition approach was found to have a great importance in the formation of nanosized carbon-based materials, such as carbon nanotubes. The chemical reaction of vapor-phase materials produces a thin coating on the surfaces of substrate in CVD. The precursor should achieve the following requirements: high chemical purity, a nonhazardous nature, volatility, good stability during evaporation, a long shelf-life, and low cost. Furthermore, no residual impurities resulted from the decomposition process (Wang et al. 2022 ).

Hydrothermal methods

One of the most important and extensively utilized methods for producing nanosized materials is the hydrothermal process. In this method, nanoparticles synthesized though a heterogeneous reaction in a liquid medium at high temperature and pressure around the critical point in a sealed vessel. This approach exhibited different advantages over others. It can produce nanosized materials with no stability at high temperature. It can also generate nanosized materials with high vapor pressure with very low loss of starting materials. Hydrothermal method is beneficially used for synthesizing nanomaterials with different morphologies, such as such as nanorods, nanowires, nanosheets, and nanospheres (Gan et al. 2020 ).

The sol–gel method

The sol–gel method is a wet-chemical process for the creation of nanomaterials that has been widely employed. It was utilized to synthesize many types of nanomaterials-based metal oxide with high quality. The sol–gel method as eco-friendly approach exhibited many other advantages, including the production of nanomaterials with homogeneity, application of low processing temperature, and a facile way to produce complex nanostructures and composites (Khan et al. 2022 ).

Application of nanomaterials in energy sector

Energy has importance role in our daily life, and it is considered as the major resource for the human activity. According to the International Energy Agency (IEA), energy demand will continue to rise until 2030. Owing to increasing energy demand, there is a great need to new technology with low energy demand as a potential way to conserve energy. Lithium-ion batteries, light-emitting diode (LED), fuel cells, ultra-capacitor, and solar cell were used to conserve the energy as they improve the efficiency and application period. Nanotechnology is expected to contribute to low-cost and efficient energy generation, transmission, and storage systems in the future. The fabrication of materials and structures with nanoscale can potentially use for producing a newly developed devices with high efficiency, low cost, and low energy demand in many applications such as hydrogen production, solar photovoltaic systems, solar thermal systems, and energy saving technologies (Christian 2013 ; Yianoulis and Giannouli 2008 ). As a result, nanotechnology’s application in the field of energy is a hot topic in many scientific fields. The current trend is being hampered by the high cost of production compared to previous technologies. To obtain higher efficiency with low production cost, the priority should be given to nanotechnology in terms of energy. As shown in Fig.  3 , piezoelectric, thermoelectric, triboelectric, catalytic, and photovoltaic are the main nanomaterials, which strongly contributed to several energy applications. Inorganic nanoparticles have superior thermal and electrical conductivity, chemical stability, and a wide surface area due to their unique properties. For the application of energy generation, nanosized materials recorded two-time thermoelectric performance higher than those of conventional materials.

Different energy applications: energy generation, storage, conversion, and saving up on nanomaterials substances (Wang et al. 2020 )

As reported by International Energy Agency (IEA), the nanomaterials with high thermal insulation and energy efficiency will lead to conserve about 20% of the current energy consumption. There are three advantages, observed from the application of nanotechnology in the production of nanosized materials for renewable energy as follows:

An improvement in the efficiency of heating and lighting,

Higher capacity of electrical storage.

A significant reduction of the pollutants resulted from the use of conventional energy resources.

In energy conversion applications, the active sites of catalytic materials improved significantly by applying nanostructuring advanced strategy. The recent advances were found to have the potential to impel further the visions of alteration the hybrid properties at the nanoscale, which could lead to produce next generation materials for energy applications. Multifunctional nanomaterials research can be defined as the study on how the structures of materials govern their properties, including their fabrication and design (Wang et al. 2020 ).

Solar cell technology, as a valuable source of renewable energy, is nevertheless somewhat costly when compared to fossil fuels used to generate power. Although solar cells have a low efficiency, with a maximum of 30 percent, the most widely used kind has a 15–20 percent efficiency ( http://www.i-sis.org.uk/QDA 2011 ). Owing to losing more than a half of their efficiency through heat up, the conventional solar cells are inefficient. Recently, adding nanomaterials, such as fullerenes, carbon nanotubes (CNTs), and quantum dots, as shown in Figs. 4 and 5 to solar cell could increase its efficiency. Basically, nanotechnology technique can be beneficially used to build up high solar cells with high efficiency and low cost. Nanoparticles exhibited the following advantages in the solar power plants: -

Because of the small particle sizes, nanomaterials can easily pass through pumps and plumbing with no adverse effects.

Owing to high ability of nanofluids to absorb energy directly, they exceeded intermediate heat transfer steps.

High optical selectivity of nanofluids (i.e., low emittance in the infrared range and high absorption in the solar range).

Solar collector with nanomaterials exhibited more uniform receiver temperature, which associated with a reduction in material constraints.

The enhancement of the heat transfer after incorporating nanoparticles, as a result of thermal conductivity and higher convection may improve receiver performance.

The efficiency of absorption could be improved by tuning the nanoparticle shape and size to the appropriate application.

Zero-dimensional carbon nanomaterials, a carbon dots, and b fullerene. One-dimensional carbon nanomaterial, c carbon nanotube. Two-dimensional carbon nanomaterial, d graphene, and e graphene oxide (Han et al. 2015 )

Evolution of photovoltaic technology: from conventional (silicon-based solar cells) to nanostructured solar cells (quantum-based and dye-sensitized solar cells) (Sharma et al. 2018 ; https://www.gamry.com/application-notes/physechem/dssc-dye-sensitized-solar-cells )

Quantum-based solar cell

As shown in Fig.  5 , the addition of quantum dot crystals to the solar cell could improve the efficiency, whereas they possess high ability to absorb and convert light into electrical energy. This design is ideal for enhancing the solar cell efficacy from the small distance between the dots. Accordingly, multi release of electrons were gained via incorporation of quantum dots for solar cells. The efficiency of converting solar energy into electrical one increased by 42%.

Dye-sensitized solar cell (DSSC):

A dye-sensitized solar cells (DSSCs) are a class of low-cost solar cells belonging to the group of environmentally friendly thin-film solar cells. They have a good efficiency (nearly 20–30%) even under low flux of sunlight. The temperature sensitivity of the liquid electrolyte is considered as the main disadvantage of this type of solar cell. Many researches are carrying out to develop the electrolyte’s performance and consequently stability of solar cell. It is based on the photoelectrochemical processes. As shown in Fig.  6 , the employing electrode is fabricated by depositing a thin layer of oxide semiconducting materials such as TiO 2 (n-type) and NiO (p-type) on a transparent conductive glass plate made of indium tin oxide (ITO). These oxides have a wide band gap in the energy range from 3 to 3.2 eV. Because it is non-toxic, less expensive, and available, TiO 2 is mostly used as a semiconducting layer. The dye is covalently attached to the surface of TiO 2 . Due to the high porosity structure and large surface area of the electrode, a large number of dye molecules are attached to the surface of the TiO 2 nanoparticles, and thus, the light absorption on the surface of the semiconductor enhances. After laying an ultra-thin coating of TiO 2 on the upper surface, the efficiency of about 18% was determined, it was shown that TiO 2 was by 50% more efficient compared to the same material without coatings (Takabayashi et al. 2004 ), and they had synthesized a thin-film electrode made of a polycrystalline Si/doped TiO 2 semiconductor. The system consists on a particulate doped TiO 2 thin film supported on the surface on inexpensive polycrystalline Si, thus allowing to the absorption of short- and long-wavelength parts of the solar light, respectively. As a result, this combination can yield a high solar-to-chemical conversion efficiency of more than 10%, which results in a very promising approach to efficient and low-cost solar energy conversion.

Dye-sensitized solar cell (Serrano et al. 2009 )

Consequently, TiO 2 reduces directly the energy cost and yields cheaper solar cells.

Organic-polymer-based PV Solar cell (OPV):

In this type, particles are excited donating free electron–hole pairs via the effective field created between two dissimilar organic materials, known as the donor and accept or molecules. This type is obtained as an inexpensive renewable energy sources for the production of energy from light at very low cost (Pelemiš et al. 2013 ).

Hot carrier solar cells

In this cell, a free electron is highly bumped into the conduction band by a too-energetic photon. Therefore, its electronic temperature becomes quite hot (as high as 3000 K). The hot electron will relax to the bottom of the conduction band, typically through a few hundred femtoseconds, passing heat to the lattice. These cells have the advantages that a high-energy electron will enhance the photovoltage of the device that will result in increasing the cell efficiency. Finally, the advantages of solar cells are as follows:

Increasing device photovoltage as well as its efficiency due to using a high-energy electron.

Thin-film solar cells are the next generation of solar cells (flexible solar panels) that use less materials at low cost and are easier to produce and install.

For example, these sheets can be incorporated into a bag that charges laptop and cell phone. It can also cover buildings windows to collect solar energy from the entire building rather than just its roof (as shown in Fig. 7 ). So, it can be suitable to use as supply power to high-rise buildings.

Solve the problem of diffusion light absorption

PV system install on a Commercial Office Building ( https://www.pointloadpower.com/articles/10-common-questions-commercial-building-owners-have-about-rooftop-solar )

Accordingly, Alamri et al. 2020 presented an investigation to improve the energy efficiency of solar PV panels using hydrophobic SiO 2 nanomaterial. They concluded that the use of SiO 2 coating for PV panels results in the better performance of the PV panels. The overall efficiency of the coated panel increased by 15% and 5%, compared to the dusty panel and the uncoated panel which was manually cleaned daily, respectively, that improve the overall efficiency and producing more efficient solar photovoltaic system.

Solar thermal collector

The solar collector is a key component of water heating systems and solar energy applications. It can be elucidated as a green heat exchanger device which converts the energy of incident solar radiation or sunlight either to electrical energy directly in PV (photovoltaic) applications, or to the thermal energy in solar thermal applications.

The performance of the solar collector is known as the ratio between the rates of useful heat (Q) transferred to a fluid and the solar radiation intensity falling on the collector surface. It was expressed previously as follows (Shaffei et al. 2021a , b ):-

where η is collector efficiency, Q is the gained energy by water (W), A c is the collector area (m 2 ), and Gt is incident solar radiation W/m 2

where η is collector efficiency, m mass of water, Cp = 4180 J/Kg o C, A c area of collector, Gt W/m 2 intensity of incident light, T i inlet temperature, and T o outlet temperature.

To increase the collector efficiency, the researchers investigated several types of nanoblack coating to maximize the amount of solar energy absorbed by the black surface and converted into heat or electricity. In solar water heating systems, scientists studied different types of selective coatings such as black paint, sol-chrome, black chrome, black nickel, and black anodized aluminum to increase the collector efficiency and saving the energy consumption. However, some of these coating is high cost and also not friendly environmental such as chrome coating (Karuppiah et al. 2000 ). Moreover, the commercial black paint is strong emitters for thermal infrared radiation at high temperature which decrease the overall collector efficiency. Accordingly, Girginov et al. 2013 stated that electrodeposition of metal ions within porous alumina results in more efficient coating. The formed anodic aluminum oxide layer (AAO) is characterized by specific structure having self-organized and more-ordered nanopores as shown clearly in Fig.  8 (Shaffei et al. 2021a , b ).

A Schematic of the ideal densely packed hexagonal array of pores; B Actual cross-sectional view of a typically synthesized AAO layer (Poinern et al. 2011 )

Shaffei et al. ( 2021a , b ) studied and tested the performance of two solar collector panels in two similar heating systems. The first system comprised the nanoblack-colored anodized aluminum solar panel and the other had black aluminum solar panel colored by commercial black paint for a comparison. The results confirmed that the nanoblack coating results in increment of the efficiency of solar heating system by approximately 12% compared with the commercial black paint.

Nanofluid-based solar collector

The nanofluid-based solar collector is a new generation of solar collectors based on nanotechnology (Hussein 2016 ), in which nanoparticles in a liquid medium scatter and absorb solar radiation.

The use of a nanofluid as a working fluid in the collector improves efficiency.

On top of the collector, a nanofluid absorbs the sun’s radiation directly.

As a result, this layer may eliminate the need for the absorber plate and tubes found in traditional solar collectors, as well as materials for both conventional and nanocollectors. The main difference between the conventional and nanofluid-based collectors lies in the mode of the working fluid heating. In the conventional collector, the sunlight is absorbed by a surface and then transmitted to the fluid (water or air), while in the nanofluid collector the sunlight is immediately absorbed by the working fluid through the radiative heat transfer as shown in Fig.  9 .

Schematics and materials for both conventional and nanocollectors

Yousefi et al. 2012 studied the effect of utilizing the (Al 2 O 3 –water) nanofluid as an absorbing medium in a flat-plate solar collector. The nanoparticles weight fraction was taken as 0.2 and 0.4%, respectively. Moreover, the particles dimension was nearly 15 nm. The results showed that, on the addition of 0.2 wt% of nanofluid, the collector efficiency is increased by 28.3% . Consequently, the collector using an alumina–water nanofluid had higher efficiency than that using the water only. Regarding the data listed in Table 2 , various types of nanofluids enhance the collector efficiency. The researchers concluded that nanoparticles increased heat-collection efficiency by up to 10 percent. (Taylor et al. 2011 ; www.sciencedaily.com/releases/2011/04/110405081910.htm ).

Limitations of nanofluids in solar collectors

The benefits of using nanofluids in solar thermal collectors include increased thermal efficiency, potential reduction in collector size, and cost-effectiveness, while nanofluids are still limited in application in collectors as the nanofluids are highly unstable and their particles tend to precipitate. Meanwhile, the nanoparticles move in Brownian motion that results in aggregation and increases the fluid viscosity. As a result, increased viscosity reduces flow rate in thermosyphons or increases pump power required in forced convection systems. Both of these will eventually reduce the system’s efficiency (Wole‑osho et al. 2020 ).

Nanostructured materials are being successfully used to increase the conversion of hydrogen energy into electricity via fuel cells. Fuel cell technologies have emerged as one of the most promising approaches to various energy resources, as well as to energy sustainability and the environment (Peterson et al. 2010 ). In a fuel cell, hydrogen and oxygen combine to form water, which produces electricity and heat. As illustrated in Fig.  10 , this occurs in an environmentally beneficial manner, with no damaging carbon dioxide (CO 2 ) emissions. Despite its many advantages, the fuel cell still has a number of disadvantages, including high cost, operability, and durability difficulties. Nanotechnology can be used to overcome these disadvantages. In practice, nanomaterials can be used in the fuel cell membrane (which is responsible for separating hydrogen into protons and electrons), the contribution of carbon nanotubes (CNTs) to improving the mechanical strength and proton conductivity of polymer electrolyte membranes, as well as catalysts and electrodes. Furthermore, storing huge amounts of hydrogen fuel is either too cumbersome or too expensive. Large amounts of hydrogen can be stored inside nanomaterials such as carbon nanotubes (CNTs) and carbon nanofibers, which is another key constraint in fuel cells. Carbon nanotube fuel cells, which are regarded the most environmentally acceptable form of energy, are currently being used to store hydrogen. Carbon nanotubes have a layered graphene tubular shape that allows them to store hydrogen efficiently. In reality, hydrogen can be adsorbed by carbon nanotubes (CNTs) by a physic-sorption phenomenon in which hydrogen is trapped in the cylindrical structure of the nanotubes or in the interstitial regions between nanotubes. Consequently, hydrogen has the best energy-to-weight ratio of any fuel and is widely utilized in space vehicles (Liu et al. 2010 ).

Hydrogen fuel cell (Bishop 2014 )

Accordingly, the application of CNTs as the catalyst support in hydrogen production appears to be effective and attractive owing to their special structural morphology and characteristics. The surface of CNTs is usually modified to create the functional groups for specific needs. Nikitin et al. 2008 stated that the hydrogenation of single-walled carbon nanotubes (SWCNTs) using atomic hydrogen as the hydrogenation agent depends on the nanotube diameter, and for the diameter values around 2.0 nm. Hence, the hydrogenation (nanotube–hydrogen complexes) was close to 100% and is stable at room temperature. This results in enhancement of hydrogen storage capacity to 7 wt%. Girishkumar et al. 2005 investigated the power density of hydrogen cell based on using single-walled carbon nanotubes (SWCNTs) support and platinum catalyst. They concluded that the maximum power density of CFE/SWCNT/Pt electrodes was nearly 20% better than CFE/CB/Pt electrodes. Also, Orinakova and Orinak 2011 stated that the storage capacity of SWNTs and MWNTs for hydrogen is lower than 1 wt% at ambient temperature, but the capacity could be raised considerably between 4 and 8 wt% when decreasing the temperature of adsorption or modifying the CNTs. Some of the experimentally reported hydrogen storage capacities for different CNTs are summarized in Table 3 . The variation in data of hydrogen storage capacity in CNT is based on their characteristics. The milled MWNTs at the same temperature and applied pressure result in increasing in hydrogen storage capacity; meanwhile, utilizing of milled MWNT may result in saving energy because there is no need for additional heating or higher pressure.

In addition, Amin et al. 2014 investigated the catalytic activity of impregnation of Ni and Pd/Ni nanoparticles on Vulcan XC-72R carbon black electrode for methanol oxidation in hydrogen cell. They tested the methanol oxidation reaction at Ni/C and Pd/Ni/C electrocatalysts in (0.2 M MeOH,‏ 0.5 M KOH) solution and concluded that Pd/Ni/C is more stable than Pd/C and Ni/C electrocatalysts. Therefore, Pd/Ni/C is a suitable as a less expensive electrocatalyst for methanol oxidation that can be beneficially applied in fuel cells. Khater et al. 2022 studied the effect of bifunctional manganese oxide–silver nanocomposites anchored on graphitic mesoporous carbon to promote oxygen reduction and inhibit cathodic biofilm growth for long-term operation of microbial fuel cells, and they concluded that MnOx–Ag/GMC nanocomposites showed high antibacterial activity in MFCs, suppressing biofilm growth on the cathode. Consequently, MFCs with MnOx–Ag/GMC nanocomposites had a much higher maximum power density (160 mW m −2 ) compared to Pt/C.

Cathode-based MFCs (60 mW m −2 ) with a much lower closed-circuit potential decay during continuous operation for 5 months. Also Xie et al. 2022 presented highly efficient, economical, and environment friendly electrocatalysts for the hydrogen and oxygen evolution reactions that is necessary for economical water splitting. FeS 2 nanoparticles were anchored on the surface of MXene through a simple adsorption-growth route (FeS2@MXene). The large active surface area of FeS 2 and its robust interfacial interaction with conductive and hydrophilic MXene nanosheets and the obtained FeS2@MXene composite can accelerate the transfer of mass/charge and facilitate contact between water molecules and reactive sites of FeS 2 . They stated that the functioned hybrid bifunctional electrocatalyst requires only a cell voltage of 1.57 V to deliver a current density of 10 mA cm −2 . The high catalytic activity of the FeS2@MXene hybrid is attributed to the well-designed structure and constructed interface between FeS 2 and MXene, which results in a larger specific surface area, facilitated mass/charge transfer, and saving energy.

Lithium-Ion batteries

Nanostructured materials have recently been proposed for use in energy storage devices, particularly those with high charge/discharge current rates, such as lithium-ion batteries, which are widely used in mobile phones and laptops (as shown in Fig.  11 ).

A Li-ion battery from a Nokia mobile phone ( https://en.wikipedia.org/wiki/Lithium-ion_battery )

Furthermore, the success of electric and hybrid electric vehicles (EVs and HEVs, respectively), which are predicted to at least partially replace conventional vehicles, is dependent on the development of energy storage devices with high power and high energy density. As a result, these energy storage solutions will rely on cutting-edge materials research, namely the development of electrode materials that can charge and discharge at high current rates. In general, nanostructure active electrode materials have the ability to increase the available power from a battery while reducing the time required to recharge it.

These advantages are obtained by coating the electrode’s surface with nanoparticles, which enhances the electrode’s surface area and allows more current to flow between the electrode and the chemicals within the battery. This technology could improve hybrid vehicle efficiency by lowering the weight of the batteries required to generate appropriate power. When the battery is not being used, nanomaterials are used to separate the liquids in the battery from the solid electrodes, extending the battery’s shelf life. This separation eliminates the low-level discharge that happens in a traditional battery, extending the battery’s shelf life significantly ( https://www.understandingnano.com/batteries.htm ).

The applications of nanotechnology in batteries are discussed as follows: -

Firstly, the modification of the active substance in the electrode material (cathode or anode) by adding nanomaterials.

Secondly, the application of nanotechnology to improve the performance of electrodes by using of nanocoatings. For example, nanodimensional additives such as nanocarbons, graphene, and carbon nanotubes have better electron conduction, or the use of nanothick coatings on the active material to prevent unwanted reactions with the electrolyte resulting the electrode stability and stress modulation. Regarding LiFePO 4 cathode, the amount of electron conductivity is poor. Hence, the conductivity is enhanced by using a conductive carbon coating on its particles or applying a conductive carbon material as an additive. Also, LiCoO 2 cathode is unstable at high currents in the vicinity of the electrolyte; for stabilization, nanothick oxide coating can be utilized. Accordingly, carbon coating increases conductivity, capacity, and consequently the cell power. However, the research in this area (to create this coating) is still insufficient. Therefore, research in the field of synthesis methods is very important (Songping et al. 2015 ).

The creation and usage of energy efficient LEDs based on inorganic and organic semiconductor materials was the first nanotechnology application in the field of lighting. LED technology has already tapped huge commercial potentials in the illumination of displays, buildings, and cars due to its compact form, flexible color scheme, and high energy yield. It was created with the purpose of enhancing the energy efficiency of LEDs by using quantum dots. Furthermore, nanoscale light-emitting particles aid in the reduction of LED scattering effects, resulting in an increase in light production. To boost particle stability, the particles must be coated (Hessian 2008 ).

As shown in Fig.  12 , LEDs are predicted to account for 87% of lighting sources by 2030, with lighting controls accounting for 50% of lighting installations in commercial buildings. In 2015, about 13% of lighting installations in the commercial sector were LED lights. Up to 91% of indoor illumination energy usage occurs in the commercial and industrial sectors.

Lead lighting share in industry ( https://www.warehouse-lighting.com/blogs/lighting-blog/led-lighting-statistics )

The high efficient nanomaterials in energy saving

Graphene is one of nanomaterials having high electrical conductivity and excellent mechanical strength. It is a super-capacitive biodegradable material that is less expensive than pure silicon. Furthermore, graphene can absorb solar energy’s ultraviolet radiation, which is ignored by Si solar cells. As a result, solar cells with a wavelength of 0.345 nm can absorb more solar light. Das et al. 2017 investigated the melting of carbon-based nanocomposites in a vertically oriented shell-tube thermal energy storage system. They looked at the effect of carbonic nanomaterial structure on the thermal behavior of n-eicosane (phase change materials (PCM): as nanofillers to improve n-alkane thermal conductivity). They investigated the effects of three structures on melting time: single-walled carbon nanotubes (SWCNT), nanodiamond, and graphene nanoplatelets. Their research found that using nanodiamond had no effect on melting time when SWCNT and graphene were used at a 1% by volume ratio. It was discovered that melting duration could be reduced by up to 15% and 25%, respectively. The improved thermal conductivity caused by the nanostructures incorporation was attributed to the shorter melting time. In addition, Hussein et al. 2021 investigated the effect of nanographene dispersion on the rate of evaporation of saline water to save energy consumption during thermal desalination and concluded that graphene is one of the best nanomaterials for maximizing heat transfer efficiency because it maximized the broken hydrogen bond between water molecules and minimized the viscosity of saline water, resulting in maximum energy savings by 30% on using 10 g/l.

The energy-saving efficiency declined as the graphene increased. Meanwhile, even though graphene breaks the hydrogen bond, the increase in saline viscosity lowers the boiling point. As a result, there is a critical dose that maximizes hydrogen bond breaking while lowering saline water viscosity. The optimum dose was determined to be 10 g of nanographene/1 L of saline water based on these findings (Hussein et al. 2021 ). Furthermore, Hussein et al. 2020 investigated the use of nanographene oxide in the thermal desalination of saline water. The generated desalinated water quantity acquired utilizing nanographene oxide was more than double that obtained using the usual thermal desalination process, resulting in a 22% energy savings.

Quantum dots

The quantum dots are mainly semiconductor crystals with nanoscale, which possess high ability to absorb and convert light into electrical energy. Owing to their small size, dots can spray onto flexible surfaces like plastic. This design is ideal for enhancing the efficacy of the small distance between the dots. The efficiency of converting solar energy into electrical one increased on applying quantum dots (Sabr et al. 2022 ). Because of its superior properties, such as thermal conductivity, metallic or semiconducting electronic behavior, and surface area, CNTs strongly contributed to the enhancement of conversion of solar energy into electricity or the generation of fuels through photocatalysis (Sharma et al. 2018 ). Experiments have already shown that quantum dots (tiny nanoparticles only a few nanometers in size) are three times more efficient at converting solar energy than the best material currently used in solar cells.

The application of nanomaterials in water and wastewater treatment has grown wide attention. Nanomaterials have high reactivity and adsorption capacities due to their unique characteristics, small diameters, and large specific surface areas. Antibacterial silver nanoparticles (Ag NPs) are effective against a variety of microorganisms, including viruses, bacteria, and fungi (Borrego et al. 2016 ). As a result, Ag NP is an effective antimicrobial agent that is widely used in water decontamination (Kalhapure et al. 2015 ). Because of their high antibacterial activity and cost-effectiveness, these nanoparticles (Ag NPs) adhered to the filter materials in the water disinfection process. Chemical reduction is also used to make Ag NPs, which are then integrated into polyethersulfone (PES) microfiltration membranes.

These PES-Ag NPs membranes have excellent antibacterial properties and are widely used in water treatment. For disinfection and biofouling reduction in domestic water treatment, Ag NPs are also integrated into ceramic materials/membranes. It is possible to improve the removal effectiveness of Escherichia coli by adding Ag NPs to ceramic filters made of clay and sawdust. Furthermore, it was discovered that filters with a higher porosity removed more germs than those with a lower porosity (Krishnaraj et al 2012 ). Furthermore, colloidal Ag NPs have been coupled with clay-rich soil-based cylindrical ceramic filters. Colloidal Ag NPs increased filter performance, and the filters can remove Escherichia coli at a rate of between 97.8 and 100% (Lu et al. 2016 ; Oyanedel-Craver and Smith 2008 ). Several types of nanomaterials applications for water and wastewater treatment are listed in Table 4 .

Nanomaterial on the solar still productivity

Solar still distillation is one of the most primitive types of water treatment that contributes to the solution of the water crisis. Solar stills, as generally known, have numerous advantages, including being simple, inexpensive, pollution-free, and requiring less maintenance. However, the freshwater yield of a conventional solar still (CSS) is restricted. As a result, researchers are attempting to improve its efficiency by employing a variety of nanomaterials. The performance of a modified solar still (MSS) can be improved by adding copper oxide nanoparticles to the black paint, for example. As the concentration of nanoparticles increases, the water productivity enhanced. Meanwhile, raising the concentration of nanomaterials increases the rate of heat transmission between the basin water and the still walls. Furthermore, as compared to CSS, using CuO nanoparticles boosts freshwater productivity by around 16% and 25% at weight fraction concentrations of 10% and 40%, respectively, as shown in Fig.  13 (Kabeel et al. 2017 ).

Layout diagram of conventional solar still and modified solar still with nanoparticles (Kabeel et al. 2017 )

Industrial application of nanomaterials

Nanotechnology was applied in many industrial activities and private sectors through the optimization of products for substantially maintaining the energy consumption.

Dust-repellent coatings with TiO 2 -based nanomolecules

The conventional applications of nano-TiO 2 -modified coatings can be effectively used to control the dirt and dust after exposure of an area to ultraviolet radiation. The system of nanoparticle delivery was developed by a new company (Swift Coat), which can be beneficially used to synthesize coatings with high efficiency in dust repellent for solar panels with less needed maintenance. It is expected that the application of such nanoparticle delivery can be successfully used in preventing solar panels soiling. The accumulation of debris, dust, and dirt on the surface’s panel with increasing time can decrease its efficiency. With more exposure time to these pollutants, the efficiency of solar cells decreases by 30%. This can result in serious problems for consumers and businesses. The installed solar panels on home’s roof could not be easily reachable by a homeowner. A continues loss in the efficiency of panels for months occurs if the homeowners cannot continuously be cleaning the panels. Similar challenges can be faced by businesses with remote solar installations. The costs of labors who clean solar panels can negatively affect. The labor’s costs for cleaning solar panels can significantly cut into the savings the company may have safeguarded by adopting a source of green energy (Newton 2021 ).

Corrosion protection

Corrosion is regarded as an important issue in the industrial world. Globally, the expected annual cost of preventing corrosion, including checking and substituting parts and shielding against corrosion—is around $2.5 trillion. Based on National Association of Corrosion Engineers (NACE), this value is equivalent to 3.4% of the global gross domestic product (GDP) in 2020. As well known, the application of industrial paints and coatings on panels act as a protected layer against corrosion. Moreover, the life span of metal parts can be extended by after coating it. Alternatives that are highly effective in resisting corrosion have been developed using nanotechnology. The use of nanotechnology has resulted in corrosion-resistant alternatives.

Paints and coatings

Graphene’s anticorrosive properties have been discovered by recent study conducted by South Australian chemicals company Technology using commercially available coatings and paints. Figure  14  shows the lattice-like structure of graphene, which is made up of carbon atoms arranged in a thin sheet. Scientists exposed steel surfaces to 1344 h of salt spray to test the power of the graphene coating and a control coating. The company claims that scribe creep improved sixfold when graphene was added to the control coatings, suggesting improved corrosion resistance. These paints and coatings were applied to smooth, cold-rolled steel as part of the company’s tests. Steel is considered to be a challenging substrate for anticorrosive coatings. Coatings tend to adhere to abrasive blast-cleaned steel more readily due to its more suitable anchor profile compared with similar substrates. Graphene coatings proved very successful for the research team, combining with other corrosion management techniques like temperature control and improved air flow to make valuable assets for industrial applications.

Structure of graphene ( https://www.graphene-info.com/graphene-structure-and-shape )

Risk of Nanomaterials

Nanoparticles can get up in the environment by mistake or as a result of their synthesis, transportation, storage, usage, or disposal. The nanoscale diameter of these particles facilitates their migration in numerous bodily areas, which can result in catastrophic illnesses such as cancer and organ damage. Furthermore, nanoparticles inhaled by an organism can easily reach the heart, liver, and blood cells via the circulation. As a result, further study is needed to close the knowledge and information gap concerning nanoparticle behavior in soil, air, and water, as well as their accumulative qualities in food chains. Because nanotechnology is still in its infancy, there are concerns regarding the impact of its industrial and commercial applications on the environment and organisms (Pandey and Jain 2020 ). Table 5 lists the overall features as well as the danger of nanoparticles.

Cost of nanomaterials

On applying nanotechnology-based treatments, distinct contributions from the purchase or synthesis of nanomaterials, energy (such as electricity necessary for photocatalysis treatments using nanoparticles, for example), and labor should all be taken into account when estimating operational costs (Kamali et al. 2019 ). Nanomaterial prices are largely dependent on the material type and desired features such as purity level (wt%), surface functionalization, and particle size. Prices for TiO 2 nanoparticles range from $0.03 per gram to $1.21 per gram, with treatment expenses ranging from $0.50 to $1.00 per gram of pollution. The cost of nanozero-valent iron (nZVI) particles has fallen as the technology for their manufacture has improved, and they are now roughly $0.05–0.10/g. In terms of manufacturing, however, micro- and bulk zero-valent iron are still significantly less expensive ($0.001/g) (Crane and Scott 2012 ). The cost of magnetite nanoparticles was predicted to be around 0.0035 €/g, according to (Simeonidis et al. 2015 ). CuO on -Al 2 O 3 is also the most cost-effective material, with an estimated treatment cost of 0.07 $ per gram of metal for an 80 percent pollution load reduction. Application of visible-light active nanoparticles such as N-TiO 2 or solar energy consumption is recommended as ideal alternative in locations where power prices are high (Yoshida et al. 2014 ).

Case studies

Case study (1) Performance Improvement of Solar Water.

Distillation System Using Nano fluid Particles (El-Ghetany et al. 2021 ).

Location The experimental pilot unit was installed in Solar Energy.

Department, National Research Centre, and Giza, Egypt.

Capacity up to 6000 L /day.

Process The technology is designed to produce freshwater.

As indicated in Fig.  15 , solar energy was used in the desalination process to gain freshwater. The water desalination system is divided into two loops: the heat transfer fluid (HTF) loop and the water loop. To transport thermal energy from the heat pipe evacuated tube collector to the thermal oil storage tank, synthetic thermal heating oil was chosen as the heat transfer fluid. It offers high resistance to thermal cracking, high heat transfer efficiency, and proper properties of heat transfer, low maintenance costs, and a long life (Fig.  16 ).

Schematic diagram of the solar water desalination system

Photographic view of a solar water desalination system using evacuated tube collector (El-Ghetany et al. 2021 )

The HTF loop is made up of four parts: an evacuated tube collector with a storage tank, a hot oil stainless steel coil immersed in a thermal storage tank of hot water that acts as a heat exchanger, a backup electric heater for auxiliary heating, and a hot oil circulation pump. After passing through the backup electric heater, the HTF is heated in the solar evacuated tube collector and the obtained thermal energy is transported to the 100 L hot water storage tank. The temperature of the pumped HTF is increased in the evacuated tube collector to between 75 and 90 degrees Celsius, and then, it is heated to 200 degrees Celsius in the hot oil auxiliary heater. On a solar water distillation system, the influence of nanoparticle concentrations of TiO 2 combined with hot oil loop was investigated to evaluate the daily water productivity with varied concentrations of TiO 2 .

Results Applying nanofluid particles (TiO 2 ) to the heat transfer fluid of the solar water distillation system improves heat transfer properties and hence boosts daily water productivity. When utilizing 100 mg/l TiO 2 nanoparticle concentration, the given system may produce 5616 L per day in the reference unit (without nanoparticle), and 7128 L per day in the case of using 100 mg/l TiO 2 nanoparticle concentration. The use of TiO 2 nanoparticles at a concentration of 100 mg/l resulted in a 26.9% increase in daily distilled water productivity. This boost in performance will improve the use of nanofluids in heat transfer loops, resulting in a higher daily rate of productivity.

Case study (2) Nanosilver-enabled composite for water treatment (Adonizio et al. 2019 ).

Location Solar energy-powered water treatment technology, developed by Quest Water Solutions Inc. (Canada).

Capacity up to 20,000 L per day.

Process A nano-enabled composite is included in a point-of-use (POU) water purification system with a two-stage filtering process that produces 10 L of clean water in 1 h; on the other hand, the second stage absorbs chemical contaminants.

The first stage It had an antibacterial unit that was in charge of eliminating viruses and germs. Nanocrystalline aluminum oxyhydroxide–chitosan composite embedded with 10–20 nm silver nanoparticles makes up the unit. Over a long length of time, the device may constantly emit regulated quantities of silver ions (40 ± 10 ppb) into natural drinking water. The antibacterial composite was created using a green synthesis approach that can be used at room temperature and does not require electricity to function.

The second stage It uses an activated carbon black filter with a nominal pore size of 4 m to filter out cysts and adsorb the organic pollutants, bacterial biomass, metals, pesticides, and other contaminants.

Results For a household of five, a cartridge containing 120 g of the nanosilver-based antimicrobial compound may supply safe drinking water for one year (assuming daily drinking water consumption of 10 L). This equates to a $2 yearly cost per household, which includes cartridge packing, media, plastic assembly, and sediment pre-filter. The unit may be readily activated by submerging it in water (natural drinking water) for 3–4 h at 70–100 degrees Celsius, which reduces the cost and increases the device’s durability.

Case study (3) Surface modification of RO membrane and spacer of Seawater desalination pilot set-up in Wukan desalination plant (Yang et al. 2009 ):

Location Pilot plant in the Wukan desalination plant at Penghu, which is one of Taiwan’s main off-shore islands.

Feed Actual sea water pretreated by cross-media sand filter and 5-mm cartridge filter.

Process The pilot plant setup was simulated to the actual process of the full-scale desalination plant. The influent was collected from the full-scale desalination plant’s sand filter unit and feed water tank storage, as indicated in Fig.  17 . The seawater was injected to pass through two (in-series 5-mm cartridge) filters then flow into a buffer tank. Then, using a high-pressure pump, RO feed was continuously pushed into one commercial flat-sheet membrane filtering machine, with feed flow rates set at 2 L/min. Throughout the testing, the system was operated in a constant pressure mode with a set pressure of 55.2 bar.

Schematics of seawater desalination pilot plant and cross-flow RO membrane cell for biofouling test (T1: feed water tank; T2: RO feed tank; T3: permeate tank; T4: concentrate tank; CF 1 , CF 2 : 5-mm cartridge filter; P 1 : pump; P 2 : high-pressure pump; P: pressure meter; F: flow rate meter; S: scale; V 1 , V 2 : ball valve; and V 3 : pressure release valve)

Surface modification of RO membrane and spacer

A simple nanosilver-coating process was used as a surface modification solution to minimize membrane biofouling on site in this case study. All of the flat-sheet RO membranes came from a spiral-wound membrane module (SW30-2514, FILMTECDOW), which is the same membrane that was utilized in the full-scale desalination plant. To enhance silver ion adsorption on the membrane sheet, it was first soaked in silver nitrate solution for thirty minutes. The membrane was then immersed in formaldehyde solution for forty minutes to initiate the reduction process. The same method was used to coat the spacer, which was separated from the same spiral-bound module.

Results In terms of permeate flow and TDS rejection, both the silver-coated membrane with uncoated spacer and the silver-coated spacer with uncoated membrane excelled the unmodified membrane and spacer. The antibacterial action of the silver-coated spacer, on the other hand, lasted longer. During the whole testing time of the silver-coated spacer test, there was essentially no cell reproduction on the membrane. Furthermore, the cells that adhered to the membrane appeared to lose activity soon. Hence, the modified membrane saving the total cost required for replacing by another units and labor cost for cleaning the unit.

Case study (4) NANOTECHNOLOGY FOR WATER TREATMENT.

Location The desalination plant in Llobregat, Barcelona, Spain (Fig. 18 ).

A picture of the desalination plant in Barcelona (Adeleye et al. 2019 )

Capacity The largest reverse osmosis-based desalination plant in Europe with an output of 200,000 cubic meters per day (Adeleye et al. 2019 ).

Process They were able to build membranes that resist biofouling better than any other membranes before because they used nanoparticles in their membrane coating. Nanotechnology was employed by nano-H 2 O to improve the permeability of their desalination membranes. They were able to develop a membrane with improved permeability of 50–100% by incorporating zeolite particles into the polyamide rejection layer.

Results Spain has adopted the NAWADES project. TFN membranes from nano-H 2 O have already been installed in Los Angeles, China, with ambitions to extend to the Middle East. Carbon nanotubes have offered a new way for water desalination, in addition to these approaches. The previous reverse osmosis processes will be replaced by these new technologies. Desalination plant efficiency will improve, resulting in the production of more clean, drinkable water. Finally, advancements in desalination technology can only contribute to the system’s long-term survival.

Conclusions

Nanotechnology has a significant impact on human life because it provides cheap and clean energy. As a result, it provides a significant evolution in several renewable energy devices used for energy storage and conversion, as well as environmentally beneficial materials. It has been demonstrated that they improve efficiencies and lower costs in a several areas. Nanomaterials promote solar photovoltaic systems, lithium-ion batteries, and fuel cells that lead to conserve about 20% of the current energy consumption. Moreover, nanomaterials demonstrated unique chemical, physical, and biological properties. Considerable energy saving potentials through the optimized products and production plants are found in nearly all branches of industry via nanotechnology. Nanofluids, nanographene, nanosilver, TiO 2 , CuO, Al 2 O 3 , and nanocomposites are potentially applied in industrial field. Nanoparticles emitted into the environment cause catastrophic illnesses such as cancer and organ damage. Furthermore, nanoparticles inhaled by an organism can easily reach the heart, liver, and blood cells via the circulation. As a result, the disposal of solid nanomaterial waste must be researched in order to maintain a clean and safe environment.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Silver nanoparticles

Polyethersulfone

Carbon nanotubes

Chemical vapor deposition

International Energy Agency

Light-emitting diode

Dye-sensitized solar cell

Indium tin oxide

Organic-polymer-based PV solar cell

Photovoltaic

Anodic aluminum oxide

Carbon dioxide

Electric vehicles

Hybrid electric vehicles

Phase change materials

Single-walled carbon nanotubes

Reverse osmosis membranes

National Renewable Energy Laboratory

Conventional solar still

Modified solar still

Global gross domestic product

National Association of Corrosion Engineers

Point of use

Part per billion

Heat transfer fluid

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Hussein, H.S. The state of the art of nanomaterials and its applications in energy saving. Bull Natl Res Cent 47 , 7 (2023). https://doi.org/10.1186/s42269-023-00984-4

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Nanomaterials: a review of emerging contaminants with potential health or environmental impact

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• Amer S. El-Kalliny 1 ,
• Mahmoud S. Abdel-Wahed 1 ,
• Adel A. El-Zahhar 2 ,
• Ibrahim A. Hamza 1 &
• Tarek A. Gad-Allah 1  

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Nanotechnologies have been advantageous in many sectors and gaining much concern due to the unique physical, chemical and biological properties of nanomaterials (NMs). We have surveyed peer-reviewed publications related to “nanotechnology”, “NMs”, “NMs water treatment”, “NMs air treatment”, and “NMs environmental risk” in the last 23 years. We found that most of the research work is focused on developing novel applications for NMs and new products with peculiar features. In contrast, there are relatively few of publications concerning NMs as environmental contaminants relative to that for NMs applications. Thus, we devoted this review for NMs as emerging environmental contaminants. The definition and classification of NMs will be presented first to demonstrate the importance of unifying the NMs definition. The information provided here should facilitate the detection, control, and regulation of NMs contaminants in the environment. The high surface-area-to-volume ratio and the reactivity of NMs contaminants cause the prediction of the chemical properties and potential toxicities of NPs to be extremely difficult; therefore, we found that there are marked knowledge gaps in the fate, impact, toxicity, and risk of NMs. Consequently, developing and modifying extraction methods, detection tools, and characterization technologies are essential for complete risk assessment of NMs contaminants in the environment. This will help also in setting regulations and standards for releasing and handling NMs as there are no specific regulations. Finally, the integrated treatment technologies are necessary for the removal of NMs contaminants in water. Also, membrane technology is recommended for NMs remediation in air.

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Introduction

Nanotechnology is one of the most exciting and fast-moving areas of science today. It has been advantageous in many sectors, like medicine, the military, electronics, food, chemicals, energy, and a wide variety of other scientific fields [ 1 , 2 , 3 ]. However, nanomaterials (NMs) are considered emerging environmental contaminants.

The word “emerging” means newly formed or prominent. Hence, the term “emerging contaminant” or generally “emerging environmental contaminants” can be demonstrated as a chemical or a material characterized by a perceived, potential or real threat to human health or the environment or by a lack of published health standards [ 4 , 5 , 6 ]. The discovery of new contamination sources or new pathways for a contaminant identifies it as emerging. Also, developing a new detection method or treatment technology for a contaminant gives the same identification as an emerging contaminant. There is a long list of environmental emerging contaminants including, but not limited to, pesticides, pharmaceuticals, personal care products, plasticizers, fragrances, flame retardants, hormones, algal toxins, siloxanes, different trace elements such as radionuclides and rare earth elements [ 7 , 8 , 9 , 10 ]. Among these different types of emerging contaminants are nanoparticles (NPs) and NMs. NMs are defined according to the International Organization for Standardization (ISO) and the European Union (EU) as a “material with any external dimension in the nanoscale or having an internal structure or surface structure in the nanoscale” [ 11 , 12 ]. Also, NPs are defined by ISO and EU as a “nano-object with all three external dimensions in the nanoscale”, where the nanoscale is the size range from approximately 100 nm [ 12 , 13 ].

As we devote this review for NMs as emerging environmental contaminants topic, a survey has been done of peer-reviewed publications related to “nanotechnology”, “NMs and NPs”, “NMs and water treatment”, “NMs and air treatment”, and “NMs and environmental risk” in the last 23 years, as shown in Figs.  1 a, b. There is an enormous increase in the number of publications in the field of nanotechnology since 2000 (Fig.  1 a). This leads to an exponential increase in NMs- and NPs-related research publications in the past decade. This is because NMs are beneficial in many fields. Figure  1 a shows that the highest number of publications used the “NMs and NPs” term, which indicates the importance of using this term for identifying the relevant articles. For example (and not limited to), NPs can be used in catalytic pollution prevention applications (e.g., metal oxides, clay materials, carbon materials, metal–organic frameworks, ultrafine noble metal, quantum dots, zero-valent metallic and bimetallic, etc.) [ 1 , 14 , 15 , 16 , 17 ] and can also be used in energy and manufacturing-related applications [ 14 , 18 ]. Consequently, this reflected an increase in the number of publications related to environmental risk (see Fig.  1 b). There are a significant number of publications related to NMs, which can be used for water and air treatment (see Fig.  1 b). This number of publications and studies is increasing. These studies have focused on different sides of NMs like their new applications as catalysts, adsorbents, disinfectants, and ion exchangers in air and water treatment technologies [ 19 , 20 , 21 , 22 ]. Figure  1 c shows the percentage of documents per subject area for the nanotechnology term. The highest percentage of documents related to nanotechnology term is for materials science (21.9%). Comparable percentages of about 15% are for physics and astronomy, engineering, and chemistry which show the attempts for increasing the applicability of nanotechnology. While nanotechnology is a potential technique for environmental remediation, environmental science only accounts for 2.3% of all research. For this context, there are few numbers of publications concerning NMs as emerging contaminants relative to that for NMs applications. Most of the research work is focused on developing new applications for NMs and new products with peculiar features.

Comparison of the number of peer-reviewed publications. (Data analysis of publications has been done using the Scopus scholar search system with the terms: a “nanotechnology”,“NMs”, and “NPs” from 2000 to January 2023, b “NMs” and “water treatment”, “NMs” and “air treatment”, and “NMs” and “environmental risk” from 2005 to January 2023, c the percentage of documents per subject area for nanotechnology term

There are some published articles about NMs as emerging contaminants from different points of view. In the following, we present some examples of them. Sébastien Sauvé and Mélanie Desrosiers presented a review about how one defines emerging contaminants in general and pointed out briefly that NMs are emerging contaminants [ 7 ]. Buzea et al. [ 23 ] reported in a review an overview of NPs and their origin, activity, and biological toxicity. Vlachogianni and Valavanidis presented an overall review of the current knowledge associated with human health and toxicity risk of the engineered NPs [ 1 ]. Also, the risk assessment of NMs with regard to ecology, human health, and the environment was presented in [ 2 , 22 , 24 ]. Several underlining technical issues were discussed by comparing the properties and behavior of manufactured NPs with anthropogenically produced NPs in the air [ 25 , 26 ]. An overview of emerging manufactured and biofuel NPs in the air was presented in [ 25 , 26 ]. In [ 27 ], a review by Peralta-Videa et al. included the most recent publications for the biennium 2008–2010 reported on risk assessment, stability and characterization, toxicity, the fate of NMs in terrestrial ecosystems, and novel engineered nanomaterials (ENMs). The methods for the detection of NMs were reported in [ 26 , 28 ]. Richardson and Ternes reported a series of review articles (2009–2017) for the analysis of emerging contaminants in water and surely NMs had a part in these reviews [ 29 , 30 , 31 , 32 , 33 ]. Jeevanandam et al. [ 34 ] have reviewed the classifications and the history of NMs and presented different sources of NPs and their toxic effects on mammalian cells and tissue.

The scientific community must pay attention to emerging contaminants in the environment. A number of important topics should be addressed, including detection and analysis techniques, treatment technologies, and risk assessments for emerging contaminants. As a result, this review article sheds light on NMs as emerging contaminants in the environment. In this paper, we describe the fate of NMs as emerging contaminants in the air, water, and soil. Also, the definition and the classification, and some examples of NMs usage will be presented. Furthermore, the routes of human exposure, ecotoxicity, health effects of NMs contaminants, and occupational health effects and safety issues will be highlighted. Finally, guidelines or regulations for NMs with the possible methods of detection and technologies for controlling NMs contaminants in the environment will be discussed.

This section presents the characteristics, classification, and examples of NMs to provide a comprehensive understanding of the type of emerging contaminants being studied. It is crucial to standardize the terminology used for particle size across nanotechnology, health, and environmental sciences [ 2 , 23 ]. The EU's definition of NMs is based on particle size, which can either be classified as NPs (smaller than 100 nm) or microparticles (MPs) (larger than 100 nm) [ 12 ]). NPs’ size is comparable to that of viruses, DNA, and proteins, while MPs’ size is comparable to cells, organelles, and larger physiological structures. The difference in size between NPs and MPs leads to unique features. The peculiar features of NMs are mainly due to the reduction of particle size to lower than 100 nm. These features include thermal stability, high strength, high conductivity, and low permeability. The reduction in particle size is responsible for increasing the surface area-to-volume ratio, which makes NMs more reactive than bulk forms of the same materials. Accordingly, it is challenging to anticipate the chemical characteristics and toxicities of NPs, even if the bulk materials they are derived from are well understood.

Material-based classification

NMs including NPs can be organized into four main material-based categories as follows [ 34 , 35 ]:

Carbon-based NMs, which contain mainly carbon such as carbon nanotubes (CNTs), carbon nanofibers (CNFs), carbon black, fullerenes (C60), graphene (Gr), and nanodiamonds [ 36 ];

Inorganic-based NMs, which mainly include metal NPs (e.g., Au and Ag), metal oxide NPs (e.g., TiO 2 and ZnO), and semiconductors (e.g., Si and ceramics);

Organic-based NMs, which are made up of mostly organic materials (e.g., liposomes, polymeric NPs, micelles, and dendrimers);

Composite-based NMs, which are multiphase NPs and nanostructured materials. The composites may be any combination of carbon-based, metal-based, or organic-based NMs with any form of metal, ceramic, or polymer bulk materials.

Dimension-based classification

NMs can be classified according to their dimensions. For that purpose, Pokropivny and Skorokhod [ 2 , 37 , 38 ] reported the most comprehensive classification of NMs. As they stated, NMs can be classified as those materials with either zero-dimension (0D) in which all three dimensions are in a nanometric range such as quantum dots in light-emitting diodes (LEDs) [ 39 ], solar cells [ 18 ], and lasers [ 40 ]; one dimension (1D) in which two dimensions are in a nanometric range such as nanowires [ 41 ], nanorods [ 42 ], and nanotubes [ 43 ]; two dimensions (2D) in which one dimension is in a nanometric range such as nanothin films [ 44 ], nanosheets [ 45 ], and nanoplates [ 46 ]; or three dimensions (3D) in which all three dimensions are outside of a nanometric range, as shown in Fig.  2 [ 45 , 47 ]. 3D NMs may consist of a group of nanofibers [ 48 ], nanotubes [ 49 ] or different distributions of NPs [ 50 ].

Classification of NMs according to their dimensions [ 51 ]

Classification of NMs based on their source

In terms of their sources, NMs can be classified into the following three types [ 52 ].

Natural NMs [ 25 ] are naturally occurring materials on the nanoscale that are produced in nature either by biological species or through anthropogenic activities. They are produced in many natural processes such as photochemical reactions, volcanic eruptions, forest fires, and simple erosion, and by plants and animals, e.g., shed skin and hair [ 23 ].

Incidental NMs [ 25 ] are generated as side products or byproducts of anthropogenic processes [ 53 , 54 ] and human activities such as trains, ships, aircraft, road vehicles, and even some natural processes such as forest fires [ 34 ].

ENMs [ 27 ] represent manufactured NMs that are deliberately produced with specific properties. They can be generated by physical , chemical or hybrid methods, such as milling (from their macro-scale counterparts) or self-assembly (from atoms and molecules). Besides, they may be discharged into the environment via either environmental and industrial applications or inappropriate handling of NMs [ 4 ]. Consumer products of various fields have been affected by ENMs such as cosmetics, textiles, food contact materials, improved diagnosis, and treatment of diseases. Also, ENMs are expected to be found with novel technologies, which are dedicated to waste remediation, the production of efficient energy storage, and advances in computer sciences [ 1 ].

The special characteristics of NMs make them potentially highly reactive in both environmental and biological systems which in turn alter the fate, the dispersion, and the toxicity of NMs, compared with their larger materials [ 55 , 56 ]. Table 1 shows some examples of NMs with their physical and chemical properties and uses.

Organisms and biological NPs-based classification

In living organisms, whether micro-sized (such as viruses, bacteria, and algae) or complex-structured (such as plants, insects, birds, animals, and humans), NPs and nanostructures are naturally formed [ 34 , 38 , 57 ]. Also, some living organisms are so small to be less than a few microns in size (e.g., viruses ranging from 10 to 400 nm and some bacteria from 30 to 700 μm) [ 23 ] and thus considered in the range of nanoscale and so-called nano-organisms. They include nanobacteria, viruses, fungi, algae, and yeast. New technologies and developments in instruments to visualize NMs help in identifying the morphology of these naturally formed nano-organisms [ 34 ].

NMs impact on the environment

The fate and transport of NMs including NPs in the environment depend on particle size, surface chemistry, as well as abiotic and biological processes in the environmental matrix. Thus, NPs may exist in a form of suspension as individual particles or aggregate into larger sized NMs. It may also be existed in a dissolving state or react with natural materials [ 45 , 58 ]. The tiny size of NPs causes slowness in their settling rate, and, consequently, they may suspend for a long time in water and air. Therefore, NPs can transfer easier and farther away than larger ones of the same material do [ 4 ].

NMs that exist in solid wastes and wastewater effluents are discharged directly or accidentally into the aquatic environment either by rainwater runoff or wind [ 59 , 60 ]. The small size also affects the mobility of NMs through porous media and makes them able to strongly attach to and agglomerate with mineral surfaces [ 61 ]. For instance, the attachment of NMs to mineral surfaces slows down their mobility in groundwater aquifers [ 62 ]. This leads to the traveling of NMs to longer distances before becoming trapped in the soil matrix, and therefore soils with high clay content tend to stabilize NMs and allow greater dispersal [ 4 ].

In urban atmospheres, diesel- and gasoline-fueled vehicles and stationary combustion sources contribute more than 36% of NPs. The natural NPs in the atmosphere are lower than that released from manufactured NPs. The health impacts of such NPs are still being investigated with regulatory concerns moving from traditional particulate matter (PM10) (˂ 10 µm) to PM5, PM2.5, and below, as the increased toxicity of the finer particles has been identified [ 59 , 63 ].

The main source of atmospheric NPs is automobile exhaust. Diesel engines release NPs of 20–130 nm whereas gasoline engines release NPs of 20–60 nm. It has been found that during diesel and gas combustion processes, CNTs and fibers are released as byproducts. More than 90% of carbon NPs present in the atmosphere are diesel-generated particles, thus pollution from vehicles is a major cause of nanoparticulate contamination in the urban atmosphere [ 34 ]. In addition to the exhausts, cigarette smoking and building demolition produce anthropogenic NPs. There are about 100,000 chemical compounds in the form of NPs in the particle size range of 10–700 nm [ 64 ]. NPs and microparticulates (˂ 10 µm) are released by the demolishing of a large building [ 65 ]. The released NPs around the site of building demolition may contain lead, glass, respirable asbestos fibers and other toxic particles from household materials [ 65 ].

Airborne ENMs in indoor air and ambient atmosphere is occurring from the production and application of ENMs. There is no specific study on the transport and fate of airborne ENMs in the ambient atmosphere [ 66 ]. However, Kalavrouziotis found that the catalytic converters, used for minimizing the emitted fumes by the car exhaust, have an emission for the platinum group elements. Due to this, these platinum group elements are emitted in the form of particulate matter and accumulate in the soil, plants, and air [ 67 ]. This particulate matter is being transported over long distances and has increased significantly especially along the roadside of highways during the last ten to fifteen years as has been detected recently. Besides, ENMs may form aggregates with dust particles [ 68 , 69 ] and behave like an aerosol in an ambient atmosphere. Also, the fate and transport of aerosol have been studied in a review article by Buzea et al. [ 23 ], which may be used to understand the behavior of airborne ENMs.

NMs in soil

In soils, natural NPs such as clays, organic matter, iron oxides, and other minerals play an important role in biogeochemical processes. Colloids in soil may enhance the movement of contaminants in soils and other porous media. The sorbed contaminants into colloids can be moved when conditions for colloidal transport are favorable [ 59 , 70 , 71 ].

Soil is considered a sink for ENMs and a possible source of groundwater contamination with such materials. Thus, it is essential to understand the transport behavior of ENMs in soil and connect that with the potential impact on the food chain and groundwater [ 66 ]. Tourinho et al. [ 61 ] presented from the literature the fate and effects of metal-based NPs (e.g., silver, zinc oxide, titanium dioxide, iron oxide) in soil. Also, surface chemistry plays an important role in the mobility of NMs in porous media. In water, for example, the coating of NMs with TiO 2 could be problematic, but not in soil [ 72 ].

NMs in water

In aquatic systems, a colloid has particles ranging from 1 nm to 1 µm. Aquatic colloids include naturally occurring materials (i.e., proteins, humic acids, fulvic acids, and peptides), and inorganic materials in colloidal form (i.e., manganese oxides and hydrous iron). These materials are important binding phases for both organic and inorganic contaminants due to their small size and large surface area per unit mass [ 59 , 73 ].

In freshwater, the NPs aggregates deposited to the bottom and accumulated slowly in the sediment; this affected negatively the benthic species. While, in the marine ecosystem, NPs will possibly accumulate in between cold and warm currents [ 74 ]. NPs in marine ecosystems could be also recycled through biota [ 59 ]. Thus, this can increase the risk of the species in the interface between cold and warm currents such as tuna [ 74 ]. Nam et al. [ 75 ] discovered that a high level of TiO 2 NPs was present in the sediment layer due to the settling of NPs in a simplified microcosm system. This system was designed to “assess the bioaccumulation of TiO 2 NPs in multiple model species”. Also, Nam et al. [ 75 ] show that engineered NPs such as TiO 2 NPs and Ag NPs can also travel through the feeding patterns of aquatic organisms. This study also showed that algal cells concentrate NPs due to the adhesion of NPs to the cell wall. Thus, the stability of ENMs in aqueous environments plays a role in their fate and transport in aqueous environments. The ENMs of large aggregates will be deposited quickly, and their transport and bioavailability will be greatly restricted [ 66 ]. In contrast, well-dispersed and small aggregates of ENMs will be widely transported and have higher chances to interact with and cause more risk to organisms. Few studies have been done on the possible existing forms of ENMs in the real natural water system [ 66 ]. However, aggregation is a common process for ENMs in water and causes a reduction of overall surface area and thus will limit the reactivity of such materials [ 66 ]. The influencing factors on the fate and transport of ENMs in an aqueous environment such as natural organic matter and pH were emphasized in an article review reported by Lin et al. [ 66 ].

The effects of NMs on wildlife species are still being conducted by research. Some research studies have reported a harmful effect on aquatic species, “trout” in particular, after being exposed to TiO 2 NPs [ 76 ]. The biodegradability of NMs is still under research investigation; for instance, some biodegradable fullerenes (e.g., C60 and C70) have been found to take several months to decompose, while metals and metal oxides are not biodegradable [ 4 ]. Zero-valent iron NPs are used for on-site remediation, yet little is known about their fate and transfer in the environment [ 4 ]. Also, simulating models can help in studying the fate of NMs in the environment. Recently, Avant et al. (2019) [ 77 ] applied the Water Quality Analysis Simulation Program 8 (WASP8) for simulating exposure concentrations of carbon-based NMs in surface waters and sediments. They studied the fate and transport of multiwalled carbon nanotubes (MWCNT), graphene oxide (GO), and reduced graphene oxide (rGO) in four aquatic ecosystems in the southeastern United States. They found that MWCNT existed predominantly in the sediments of the river and seepage lake. They estimated that the recovery periods would be 37 years for lakes and 1‒4 years for rivers to reduce sediment NM concentrations by 50% suggesting that carbon-based NMs have the potential for long-term ecological effects. Exposure to NMs is currently being explored and these may enter the air, water, and soil media from different routes. Thus, the routes of human exposure to such materials will be described in the following section.

The interaction of NPs with biosystem

NPs can be located inside the cell in many locations such as cell membrane, cytoplasm, lipid vesicles, or within the nucleus, and hence can damage DNA or cause cell death [ 23 , 78 , 79 ]. The contact between NPs and cell membranes is a vital step before cellular uptake. The mechanism of cell uptake of NPs is assumed as adhesive interaction by Van der Waals forces, steric interactions, electrostatic charges, or interfacial tension effects [ 80 ]. Scientific Committee on Emerging and Newly Identified Health Risks, 2006, reported the effects of NPs properties on the interaction with living organisms, and a summary of these effects is presented below [ 80 ].

The effect of NPs surface

The surface characteristics of NPs play a crucial role in NP-cell interactions and solubility. Altering the surface coating of NPs might affect their cytotoxic characteristics by affecting pharmacokinetics, diffusion, accumulation, and toxicity [ 81 ]. Colloidal behavior occurs as a consequence of changes in NP shape and size in the surface charge of the organism. It determines the response of the organism to NP shape and size in the form of cellular accumulation. It has been shown that surface chemistry affects NPs' absorption, colloidal behavior, plasma protein binding, and their ability to cross the blood–brain barrier. Also, a higher surface charge increases the cytotoxicity of NPs due to greater endocytic uptake [ 82 ]. There is therefore some evidence to suggest that positively charged NPs tend to accumulate more in tumors than negatively charged NPs, possibly as positively charged density is more easily separated in the interstitial space and, as a result, taken by tumor cells [ 83 ]. Also, due to the presence of negatively charged proteins on the outer membrane of gastrointestinal epithelial cells, positively charged NPs are more permeable to the gastrointestinal mucous barrier than neutral and negatively charged NPs [ 84 ]. Another significant variable that has an impact on pharmacokinetics and biodistribution is hydrophobicity. Plasma proteins tend to be absorbed by NPs that have two or more hydrophobic surfaces, resulting in a shorter bloodstream retention time [ 85 ].

The effects of size and shape of NPs

Size and shape of NPs affect biodistribution, kinetics of release, and cellular uptake of NPs. Generally, NPs are brought into cells through the three most significant mechanisms: phagocytosis, diffusion, and fluid phase endocytosis.

Because of their small size, NPs are frequently misidentified as foreign agents by macrophages; however, MPs easily are taken up by reticuloendothelial systems [ 86 ]. The surface area of the particles increases as their size decreases, and a larger surface area facilitates particle diffusion into cells. For instance, a study conducted by Donkor and Tang [ 87 ] found that 30 nm single-walled carbon nanotubes (SWNT) were more likely to be internalized by cells and nuclei than 50 nm SWNT. Previous studies have shown that, when the diameter increases to 500 nm, caveolae-mediated processes (endocytosis) become dominant in the cellular internalization of microspheres coated with clathrin [ 88 ]. Additionally, NPs of 50 nm diameter target and act on human mesenchymal stem cells without endocytosis [ 89 ]. Although NPs larger than 1 m are difficult to directly enter cells, they can interact with proteins that are taken up by the cells. NPs larger than 6 nm are incapable of being eliminated by the body leading to their accumulation in some organs [ 90 ]. Studies on the bio-distribution and bioaccumulation of AuNP of various sizes in the blood were conducted showing that smaller ones accumulated more significantly in all organs and stayed longer in the blood circulation [ 91 ]. Similarly, regardless of the sort of functional groups on the particle surface, cellular uptake of NPs increases in cancer cells as they become smaller [ 92 ]. For instance, the capacity of a cell to uptake a carbon nanotube depends on its length. Compared to longer ones, submicron multiwall carbon nanotubes have demonstrated more effective cell penetration [ 93 ].

On the other hand, NPs can be found in a variety of forms as mentioned before, this might also have an impact on how they are eliminated, internalized, and endocytosed. For instance, it has been proposed that spherical NPs internalize more quickly and easily by endocytosis than rod-shaped NPs, which is consistent with the longer membrane wrapping time needed for the elongated particles. Compared to spherical NPs, the elongated NPs are more effective at adhering to the cells, this is because only a small portion of the binding sites on spherical particles may bind with target cell receptors due to their curved form. While the surface area of the longer NPs facilitates their multivalent interaction with the cell surface [ 94 ]. Sharp-shaped NPs can pass through endosome membranes and enter the cytoplasm. As a result, their exocytosis was relatively lower than that of spherical particles. Whereas, ellipsoidal NPs have lower cell absorption than spherical NPs [ 95 ].

Effect of medium/corona

When NPs reach a biological fluid like serum, their surface soon becomes covered with a coating of biomolecules such as proteins and lipids, with different affinity interactions [ 96 ]. These biomolecules, known as bio-corona, have been shown to have a significant influence on the biological activities of NPs, including complement activation, bio-distribution, contact with cell surface receptors, and cellular absorption of NPs [ 97 ]. NP physicochemical characteristics can influence the kind of corona. The production of the biomolecular corona is related to the size and surface modification of NPs. Further, biomolecule adsorption might cause NPs to grow in size, altering their pharmacokinetic and therapeutic efficacy in vivo.

Depending on how long the protein exchanges last, the protein corona is divided into hard and soft categories. A layer of proteins with strong affinity and a slow rate of exchange is called the hard corona. As the layer that is closest to the NP surface, the hard corona proteins are particularly prone to irreversible, thermodynamically advantageous conformational changes based on the chemistry of functionalization, the hydrophobic or hydrophilic properties of the proximal biological fluid, and the temperature [ 98 ]. The soft corona is a low affinity layer of proteins that exchange rapidly over time. Soft corona is indirectly connected to the NP via a certain (low) degree of biomolecule interactions.

Depending on the mode of administration, NPs are exposed to interactions with various biomolecules. As a result, protein concentration, particle size, NM type, and surface properties all have a role in defining biomolecule layers and protein corona density [ 99 ]. Another important aspect influencing protein corona formation is the biological environment, which includes media components, temperature, pH, and the physiological state of the medium. Therefore, understanding the link between many features of NMs and a specific biological environment is critical for understanding their stability, persistence, and behavior in the biological environment [ 98 ].

The development of NP protein corona complex can impact cellular absorption of NPs. The cellular absorption of NPs can be hindered by changes in the structure of adsorbed proteins. Furthermore, the unfolding of the adsorbed protein corona may influence NP accessibility to surface receptors. Moreover, the cellular attachment of NP protein complexes is a non-specific process that is dependent on the amount of adsorbed proteins rather than the kind of protein on the surface of the NPs [ 100 ].

Solubility and persistence of NPs

There is a considerable solubility for many NPs and, therefore, their interaction with the living system is close to that with bulk chemical agents. Thus, the toxicological testing procedures can be well applied to that type of NPs. The biological effects of biodegradable NPs are influenced by NP structure and degradation byproducts. NPs with very low solubility or degradability, in contrast, could accumulate within biological systems and remain there for extended periods of time. These types of NPs must have the greatest concern [ 80 , 101 ]. NPs are cleared from the human body via the renal and hepatobiliary transport system, which need to be completed in an appropriate time for clinical approval. The drug conjugated NPs therefore have to be engineered to avoid rapid elimination and prolonged body maintenance.

Ways of human exposure to NPs

Human exposure to NMs depends on the source and activities of the person. It may occur through inhalation, skin absorption, ingestion or injection. The most widely recognized route of human exposure is inhalation at the workplace [ 4 ]. Due to their small particle size, NMs can pass through both the blood–brain barrier (BBB) and the placenta. Liu et al. showed that TiO 2 NPs may pass the BBB of mice when injected with high doses [ 102 , 103 ]. Figure  3 shows two categories, primary and secondary, for the effects of NP exposure [ 104 ]. This categorization depends on the extent of exposure. Primary effects come from direct cellular NP contact. They may include toxicity, oxidative stress, DNA damage, and inflammation. Secondary NP exposure results from the translocation of NPs through tissue barriers into the blood, where they can circulate and eventually deposit in other organs. They may include toxicity at the site of NP deposition, in organs such as the liver, spleen or kidneys [ 104 ].

Routes and potential detrimental effects of NP exposure

Inhalation, ingestion, and dermal exposure routes occur through external NP sources, while internal exposure can happen when orthopedic or surgical implant wear NPs are released locally from the implant site [ 104 ]. Recently, CNTs of anthropogenic origin were found in the bronchoalveolar lavage fluids of asthmatic Parisian children. The results suggested that there is routine human exposure to CNTs [ 34 ]. Azarmi et al. [ 53 ] studied the exposure levels of operatives on-site and the dispersion of ultrafine particles (˂ 100 nm) into the surrounding environment of building activities during the mixing of fresh concrete and the subsequent drilling and cutting of hardened concrete. This research article is considered as a step toward establishing number and mass emission inventories for particle exposure during construction activities.

Animal and human studies suggest that alveolar translocation of NPs leads to circulatory access. Then, NPs distribute throughout the body, including the vasculature, heart and they may reach the liver and spleen, the two major organs for detoxification, and bone marrow. However, the extent of extrapulmonary translocation mainly depends on particle size, surface characteristics, and chemical composition of NPs [ 105 ]. The inhaled carbon NMs by humans remain in the lung, less than 1 percent of the inhaled dose may reach the circulatory system [ 106 ].

Dermal exposure to NMs can happen by using the products of sunscreen (e.g., TiO 2 and ZnO). This level of exposure depends on the condition of the skin and the characteristics of the sunscreen. NM migration to the dermis may be prevented in the case of healthy skin. In contrast, NMs can penetrate the dermis and access regional lymph nodes in the case of damaged skin, as suggested by quantum dots and nanosilver [ 105 , 107 ]. Ingestion exposure may also occur from consuming NMs contained in drinking water or food (e.g., fish) [ 62 ]. The pathways of exposure to NMs and a summary of the possible adverse health effects associated with inhalation, ingestion, and contact with NPs were presented in Fig.  4 [ 23 ]. Also, the entry mechanisms of inorganic NPs in the human body, such as TiO 2 NPs, SiO 2 NPs, ZnO NPs, Ag NPs, Au NPs, and quantum dots NPs, have been reviewed by De Matteis [ 108 ]. In this context, there is a broad range of applications for TiO 2 NPs and ZnO NPs in commercial products such as sunscreens, food additives, and paints. In addition to food and water disinfectants, Ag NPs are commonly used in the textile industries, diagnostic biosensors, imaging probes, and conductive inks. Therefore, they can enter the human body through inhalation, ingestion, and skin penetration. The majority of AuNP applications are in the medical field; photothermal therapy, bioimaging, and drug delivery are some of the most important ones. SiO 2  NPs are found in food, powders, and healthcare items such as toothpastes, detergents, and cosmetics [ 109 ].

Schematics of the human body with pathways of exposure to NPs, affected organs, and associated diseases from epidemiological, in vivo and in vitro studies. Reprinted with permission from [ 23 ] . Copyright [2007] , American Vacuum Society."

Ecotoxicity of NMs

Little is known about the physiological responses to NPs. However, some conventional ecotoxicity and toxicity tests are useful for evaluating the hazards of NPs [ 80 , 103 ]. For instance, Oberdörster [ 109 ] reported the toxicity of ENMs (e.g., fullerenes, C60). It was found that the LC50 (for 48 h) in Daphnia magna for fullerenes C60 is 800 µg/L. Also, Yamakoshi et al. [ 110 ] presented the bactericidal properties of fullerenes. There are a considerable large number of human toxicology studies as presented below. These studies demonstrate the uptake and effects of NPs at a cellular level, which can hold for species other than humans. However, the existing test methods for toxicity need modification and development [ 80 ].

Ecotoxicological effects of NMs have attracted attention since the pioneer study performed by Oberdörster [ 109 ]. In 2010, Stone et al. did a comprehensive nano-ecotoxicity survey covering 89 studies conducted between 2004 and 2009. After 12 years in 2021, the number of publications increased 69 times [ 111 ] indicating the importance of this topic. Therefore, the organization for economic co-operation and development (OECD) has recently released a guidance document for the toxicological testing of NMs in an aqueous environment and sediment [ 112 ].

Many ecotoxicological studies have not only followed the test guides (TGs) provided by OECD but also tried to improve those TGs. For instance, as an attempt to overcome the agglomeration phenomenon when manufactured NMs are mixed with algae in a culture medium for ecotoxicity tests, a dispersion method has been developed in terms of the type of dispersant, sonication time, and stirring speed [ 113 ]. The developed method was applied for 14 types of manufactured NMs specified by the OECD, namely aluminum oxide (Al 2 O 3 ), carbon black, single-walled carbon nanotubes (SWCNTs), multiwalled carbon nanotubes (MWCNTs), cerium oxide (CeO 2 ), dendrimers, fullerene, gold (Au), iron (Fe), nanoclays, silver (Ag), silicon dioxide (SiO 2 ), titanium dioxide (TiO 2 ), and zinc oxide (ZnO). The toxicity was measured through cell counts using  Raphidocelis subcapitata . The half-maximal effective concentrations (EC50) were 18.0 ± 4.6 mg/L for SWCNTs and 316.6 ± 64.7 mg/L for TiO 2 . In addition, Pengiran et al. [ 114 ] have evaluated the acute toxicity of kenaf cellulose nanofiber (CNF) against  Daphnia magna  and  Danio rerio following OECD Test No. 202: Daphnia sp. acute immobilization test. The EC 50  and LC 50  for  Daphnia magna  and  Danio rerio  were above 100 mg/L and classified as nonhazardous to the aquatic environment according to the Globally Harmonized System (GHS).

Silver NMs (Ag NM) have been engaged intensively in consumer products as antibacterial agents, which results in their occurrence in sewage sludge, and subsequently accumulated in the agricultural soils when sewage sludge is implemented as fertilizer. Accordingly, the toxicity of Ag NM in soil was assessed against the inhibition of ammonium-oxidizing bacteria (AOB) [ 115 ]. However, not much toxicity was observed for Ag NM. The aquatic ecotoxicity of manufactured silica NMs and their interactions with organic pollutants has been also studied in different studies [ 116 , 117 , 118 ]. In their studies, they investigated the ecotoxicity of nine silica NMs with different size, charge, surface modification, and shape in experiments with bacteria ( Pseudomonas putida ), algae ( Raphidocelis subcapitata ), crustacean ( Daphnia magna ), and fish gill cells ( Oncorhynchus mykiss ). The output of their studies is summarized in Table 2 . As indicated in this table, the toxicity is dependent on the surface area, surface chemistry, and exposed organism/cell type.

Unfortunately, the scattered data in the literature makes it difficult to have clear information about the ecotoxicity of NMs. This is because NMs have a wide range of properties affecting their interaction with the tested organisms.

The health effects of NMs

The scientific data for NMs that may present adverse health effects to humans under realistic exposure scenarios are not sufficient. However, NMs can induce different levels of cell injury and oxidative stress depending on their charge and particle size. Also, surface excitation by UV light can modify the surface properties, aggregation, and biological effects of NMs [ 103 , 105 , 119 ]. NMs can form reactive oxygen species (ROS), which can lead to cell membrane damage upon contact. The lipid peroxidation process is happened by ROS, which can oxidize double bonds on fatty acid tails of membrane phospholipids. This process increases the permeability of the membrane, making cells more susceptible to osmotic stress or hindering nutrient uptake. It also activates reactions that generate other free radicals, leading to more cell membrane and DNA damage [ 59 ]. Moreover, the uptake-and-damage increases when cultured cells are exposed to NMs of various metals (e.g., Fe, Mn, and Co) with TiO 2 containing SiO 2 NPs and the corresponding pure oxides. Experiments elucidated the role of NPs as carriers for heavy metal uptake. NMs may be absorbed and gain access to tissues that metals alone cannot normally reach in an uptake-and-damage mechanism called the “Trojan Horse effect” [ 120 ]. Also, the accumulation of ROS in tissue was demonstrated by Mao et al. [ 121 ] A variety of ROS-mediated stress responses could be caused by Ag NPs, including apoptosis, DNA damage, and autophagy.

Quantum dots NPs are made of cadmium or lead, which are well-known toxins. The protective coatings of quantum dots can degrade in light and oxidative conditions, releasing these toxic metals into cells and organisms and causing toxic effects [ 122 ]. However, estimates of the releases of these metals from NMs are very crude [ 59 ]. In the case of immunotoxicity, research has shown that NPs can stimulate and/or suppress immune responses by binding to proteins in the blood [ 123 ].

Some of the health problems were observed in humans due to high exposure to exhaust, where automobile exhaust is major in densely-populated cities, such as cardiopulmonary mortality; childhood cancers due to prenatal and postnatal exposure to exhaust; myocardial infarction; and proinflammatory, prothrombotic, and hemolytic responses [ 34 ]. The relation between these health problems and NPs is demonstrated by concentration measurements of NPs near highways, where the concentration decreases exponentially over several hundred meters from the traffic [ 124 ]. Besides, the CNTs of anthropogenic origin can cause granulomatous reactions, oxidative stress, and inflammation, leading to fibroplasia and neoplasia in the lungs [ 125 ]. Also, a polynuclear aromatic (benzo[a]pyrene) exists in diesel exhaust, which makes it more toxic than those gas engine exhausts [ 126 ].

Cigarette smoke, containing NPs, can lead to chronic respiratory illness, cardiovascular disease, pancreatic cancer, genetic alterations, middle ear disease, and exacerbated asthma [ 34 ].

On the other hand, biological NPs, or nanobacteria, are pervasive within organisms, animals, and humans as they are identified in serum, blood, and organs. They are suspected to cause calcifications diseases such as artery plaque, heart valves, aortic aneurysms, chronic prostatitis, renal stone formation, ovarian, and breast tumors [ 23 ]. There are evidence that nanobacteria may act as nucleation sites for stone formation or plaque, while the exact mechanisms relating nanobacteria to these above diseases are unknown [ 127 ]. Also, diatoms have a health risk to workers in diatomaceous earth mining and processing [ 128 ]. Also, biogenic magnetite is related to neurodegenerative diseases [ 129 ].

Occupational health and safety issues

The most extensive exposure to hazards is most likely to occur in the working environment. Therefore, it is expected that workers in nanotechnology-related industries and small workshops are intensively exposed to ENMs. Workers in nanotechnology-related industries and small workshops are exposed to ENMs. These NMs are characterized by novel sizes, shapes, and physical and chemical properties. Therefore, occupational toxicologists are the first to discover adverse effects on the occupational health and safety of ENMs [ 1 , 130 ]. During the processes of manufacturing, NPs can penetrate the respiratory system and via the blood can move into other organs. Also, other indications were shown by studies that NPs can penetrate through the skin [ 1 ]. The ENMs (e.g., MWCNTs) have a risk involved by pulmonary exposure. Abdominal mesothelioma was observed in mice by MWCNTs exposure and was typically recorded for workers exposed to asbestos in the past [ 131 ].

There are many actions to minimize NPs’ risk for workers. For example, personal protective equipment and engineering controls are recommended by the National Institute of Occupational Safety and Health (NIOSH), USA, to significantly decrease workplace exposure to CNFs and CNTs. According to the available information on health risks, developing prevention strategies seem to be crucial to minimize NMs exposure in the workplace such as exhaust ventilation, enclosure, and respirators, as well as worker training for good handling practices. In the UK, the safe use and handling of manufactured NMs are controlled by a framework for occupational health and safety in the workplaces done by the Health and Safety Executive (HSE) [ 1 ].

Guidelines or regulations for NMs

NMs are accompanied by many characteristics such as high chemical and biological reactivity. Also, they have cellular, tissue, and organ penetration ability. These features make them environmental contaminants. However, there is no international regulation for NMs environmental contaminants. There are also no specific federal standards for NMs’ size [ 132 ]. However, some federal statutes apply to NMs depending on the specific media of application or release [ 4 ]. Table 3 presents some federal standards and guidelines for NMs [ 6 ].

The available methods for detection and characterization of NMs

Due to the unique chemical and physical properties of NMs (such as their size, structure, surface charge, and interactions in the environment), their detection, extraction, as well as analysis are considered a big challenge [ 4 , 6 ]. Scientists focused on the environmental research of NMs, especially their fate, transport, and toxicological effects. They realized from the obtained results that their studies were hampered by a lack of adequate analytical techniques for the analysis at environmentally relevant concentrations in complex media. The conventional analytical techniques are not suitable for the physicochemical forms of NMs. Thus, it is essential to increase the number of research articles related to NMs with the development of techniques for extraction, cleanup, separation, and sample storage, increase sensitivity, and add specificity to analytical techniques [ 1 , 2 ].

Analysis methods of NMs contaminants and environmental elements in environmental samples often include multiple technologies such as size separation mechanisms, particle counting systems, and morphological and/or chemical analysis technologies. Aerosol fractionation technologies are used to obtain NMs size fractions based on their mobility properties in an electrical field. Also, aerosol mass spectrometers are used in the chemical analysis of NMs suspended in gases and liquids through vaporization and analysis of the resulting ions [ 4 ]. NMs densities in gas suspension can be determined by Expansion Condensation Nucleus Counters with a detection limit of 3 nm through adiabatic expansion followed by optical measurement [ 133 ].

The extraction and size fractionation of NMs from liquid environmental samples can be done by size exclusion chromatography, ultrafiltration, and field flow fractionation. For further analysis of fractions of NMs, dynamic light scattering and mass spectrometry are used for size analysis and chemical characterization, respectively. Besides, for determining the size and shape of NMs (˂ 10 nm) we may use Scanning Electron Microscope (SEM) and/or Transmission Electron Microscope (TEM); and getting their morphological features in air and liquid media the Atomic Force Microscopy (AFM) is used. Moreover, for measuring the crystalline phase and determining the surface chemical composition and functionality of NMs, an X-ray diffractometer and X-ray photoelectron spectrometer are used respectively [ 4 ]. Finally, it is essential to develop and invent new methods and techniques for analyzing NMs contaminants in environmental samples.

Technologies for controlling NMs contaminants in the environment

Groso et al. [ 134 ] adopted the application of the precautionary principle, especially with NMs. This is due to a lack of information that describes the health and environmental risk of engineered NPs or NMs, despite numerous discussions, reviews, and reports about nanotechnology [ 135 ]. Far from the management principles for controlling NMs in the environment, this review is focusing on the way for the treatment of these NMs to decrease their risk.

NMs are generally characterized by a high surface-to-volume ratio, which causes NPs to be extremely reactive. This high reactivity is one reason that makes NPs even much more harmful to the whole ecosystem, but at the same time facilitates methods of removing NPs contaminants. Metals and metal oxides are the most common NPs. They agglomerated with metallic quantum dots to form much larger particles, which can then be easily filtered out from the water in a conventional water treatment plant [ 135 , 136 ]. NMs may be removed from groundwater, surface water, and drinking water by the processes of sand filtration, sedimentation, and flocculation [ 62 ]. It was found that there was a significant positive effect of an anionic sodium dodecyl sulfate and a nonionic nonylphenol ethoxylate, on ZnO NPs adsorption, aggregation, dissolution, and removal by the coagulation process [ 137 ]. Kirkegaard et al. [ 138 ] assessed tap water concentrations of the NPs (i.e., Ag, TiO 2 , and ZnO) by mass flow analyses of two wastewater treatment concepts: (1) advanced membrane treatment and (2) bank infiltration. They found that aggregation, sedimentation, coagulation, and biosorption were the main removal mechanisms of NPs in water. Thus, conventional biological treatment processes are effective barriers against NPs. They also noticed that the removal efficiency of advanced technologies [i.e., microfiltration (MF) and ultrafiltration (UF)] for ZnO NPs or Zn + was low which could be mainly due to the hydrolysis or dissolution of ZnO NPs.

Removal of NMs can be done also by the adsorption process. For instance, metal NPs, in a colloidal solution of Mn, Cu, Zn, Ag + Ag 2 O, can be treated by adsorption with aquatic plants Pistia stratiotes L. and Salvinia natans L. [ 139 ], while complete removals of both ZnO NPs and CuO NPs in both single and binary suspensions from water were achieved by adsorption on activated carbon [ 140 ].

Adsorption and flocculation processes depend mainly on NPs surface charge, while membrane technology depends not only on the surface charge but also on the size of NPs. Membrane technologies get adapted in both aqueous and air media. Thus, it can play an important role in the removal of NMs emerging contaminants in the environment. Figure  5 shows the removal possibilities of water pollutants using different filtration technologies which are based on the size exclusion mechanism. According to the membrane pore diameter, UF is more effective for the removal of NPs. Nanofiltration (NF) and reverse osmosis (RO) are effective membrane filtration for NPs lower than 2 nm. However, the main drawback of such technology is the membrane fouling, which needs more efforts to solve this problem to increase the membrane lifetime and to decrease the treatment process cost.

Removal possibilities of water pollutants using different filtration technologies

Air filters and respirators are used to effectively remove NMs from the air [ 62 ]. The effective removal of NPs by fibrous filters has been previously reviewed [ 141 ].

Conclusions and recommendations

Due to the involvement of nanotechnology in different sectors such as medicine, military, electronics, food, chemicals, energy, and a great variety of other scientific fields, it is so important to classify NMs and to unify the terms used for describing particle size. This will help scientists in the field of nanotechnology, health, and environmental sciences to easily determine the methods of detecting, controlling, and regulating NMs contaminants in the environment.

NMs are mainly characterized by a very small size (˂ 100 nm), which is responsible for increasing the surface area-to-volume ratio. This makes NMs more reactive than bulk forms of the same materials. Thus, predicting the chemical properties and potential toxicities of NPs is extremely difficult. Accordingly, it is necessary to develop detection and characterization methods for NMs to well define the properties of materials in nanoscale. This will help in detecting the mechanisms of NPs’ interaction with different environmental media and with living organisms. These mechanisms of interaction are essential for determining the fate, transport, and toxicity of environmental NMs contaminants.

The reactivity of NMs contaminants in the environment with different matrices leads to a recommendation for developing the extraction methods in terms of efficiency and simplicity. However, the cost of extraction methods should be taken into consideration as well.

There is a considerable large number of studies on human toxicity of NPs at a cellular level, which can hold for species other than humans. Thus, it is recommended not only to improve the existing test methods for toxicity but also to look for different species to have a full picture for the NPs’ impact in different environmental media and set specific standards and regulations for releasing.

In the case of emerging NMs, it is recommended to conduct risk assessment including the toxicity, exposure routes, environmental fate, transport, persistence, transformation, and recycling. Analysis of the life cycle will be useful for assessing the actual environmental impacts. Also, for manufacturing new NMs, it is essential to provide an effective strategy for recycling and recovery.

In the case of ENMs, adopting the application of the precautionary principle helps decrease the health and environmental risk of such materials. Also, following up the regulations concerning the use and handling of ENMs especially in the area of manufacturing will help a lot in decreasing their risk.

Due to the complexity of NMs, multiple analysis tools are recommended to have a complete picture of the analyte. This complexity leads us also to consider using the integration systems in the removal of NMs from water. For instance, flocculation and coagulation or adsorption should be integrated with a membrane technology to target the dissolved and suspended NMs at the same time. Moreover, membrane technology is recommended as a promising tool for the removal of NMs from the air.

Indeed, there are limited data on the fate, impact, toxicity, and risk of NMs; therefore, further research is essential to fill in this gap. Besides the setting of specific regulations and standards for NMs, it is necessary to minimize the release in the environment and to decrease the risk of handling and using these materials.

Developing an effective strategy for recycling and recovery of new NMs is crucial to mitigate potential negative impacts. An analysis of their life cycle can also assist in evaluating real environmental effects if NMs are released into the environment.

Data availability

All data produced or analyzed during this study are included in this published article.

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• Published: 05 March 2019

Nanomaterials definition matters

Nature Nanotechnology volume  14 ,  page 193 ( 2019 ) Cite this article

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The definition and classification of nanomaterials in regulations leave too much room for interpretation.

Defining what we mean by a nanomaterial is never straightforward. For some, the size of the material should be a few nanometres, for others it should be smaller than a few tens of nanometres, for still others anything less than a micrometre will do. Also, for some, one dimension at the nanoscale is enough; for others it should be at least two or even all three.

For different compounds, the properties that distinguish a nanoscale specimen from its bulk correspondent occur at different sizes. The transition is rarely abrupt, and the properties evolve from bulk to nanoscale in a continuous way, so that establishing a threshold size is arbitrary. Finally, the physical and chemical properties of nanomaterials, as well as environmental and health toxicity, depend on the precise shape and composition as well as size.

All the above elements make finding a universal definition and classification an impossible task, especially if compared with chemicals that can in principle be classified just according to their formula. This presents serious challenges to regulations of products that include nanomaterials, especially in light of the real or perceived risks that nanomaterials pose to the environment or to human health. In a Perspective article in this issue , Antonia Praetorius and colleagues examine the problems with the nanomaterials definition and classification in regulations, focusing in particular on EU documents.

The main documents analysed are the European Commission’s so-called Recommendation 2011 (which established non-binding guidelines for the classification of nanomaterials), the Novel Food Regulation, the Cosmetics Regulation and the Biocide Regulation. A focus of all definitions in these documents is the size range between 1 nm and 100 nm. Because the nanoparticles present in a material are distributed in size, an additional challenge for regulations is deciding how many of the particles should fall within the defined criteria for the materials to be classified as a nanomaterial. Both the Recommendation 2011 and the Biocide Regulation describe a nanomaterial as a material that contains at least 50% of the particles (by number) in the 1–100 nm range. Because of the difficulties in reliably quantifying components at the lower end of that range, however, such a definition can easily lead to errors. For this reason, the authors suggest adopting a weight-based threshold for the size distribution, as applied for example by the US Environmental Protection Agency, rather than a number-based approach.

Perhaps most importantly, Praetorius and colleagues emphasize the presence of terms in definitions that can lead to freedom of interpretation and therefore difficulty in law application: for example the use of the terms “insoluble” or “biopersistent” to define nanomaterials in the Cosmetics Regulation, which is too ambiguous. Furthermore, the classification as nanomaterials of particles larger than 100 nm that retain properties characteristic of the nanoscale means very little without a definition of what those properties are.

Very likely, a degree of ambiguity in the definition and classification of nanomaterials will always persist. For scientific purposes this is not necessarily a major problem, provided that both researchers involved in a study and colleagues in the field understand each other. But for regulatory purposes it is problematic because defining an effective and reliable framework is essential for a successful (and safe) use of nanomaterials outside research. The ultimate solution may rely on abandoning generic definitions of nanomaterials and focus on the specific properties and potential hazard of every substance included in a product, as determined by their chemical composition, shape and size. Achieving this for every substance is unfeasible at present, so analyses and suggestions like those by Praetorius and colleagues are the best way forward.

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SYSTEMATIC REVIEW article

Current trends and emerging patterns in the application of nanomaterials for ovarian cancer research: a bibliometric analysis.

• 1 Department of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, China
• 2 State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, China

Introduction: Ovarian cancer remains to be a significant cause of global cancer-related mortality. In recent years, there has been a surge of studies in investigating the application of nanomaterials in the diagnosis and treatment of ovarian cancer. This study aims to conduct a comprehensive bibliometric analysis regarding nanomaterial-based researches on ovarian cancer to evaluate the current state and emerging patterns in this field.

Methods: A thorough literature search on the Web of Science Core Collection database was conducted to identify articles focused on nanomaterial-based ovarian cancer researches. The studies that met the inclusion criteria were selected for further analysis. VOSviewer and CiteSpace were applied for the bibliometric and visual analyses of the selected publications.

Results: A total of 2,426 studies were included in this study. The number of annual publications showed a consistent upward trend from 2003 to 2023. Notably, China, the United States, and India have emerged as the leading contributors in this field, accounting for 37.39%, 34.04%, and 5.69% of the publications, respectively. The Chinese Academy of Sciences and Anil K. Sood were identified as the most influential institution and author, respectively. Furthermore, the International Journal of Nanomedicine was the most frequently cited journal. In terms of the research focus, significant attention has been directed towards nanomaterial-related drug delivery, while the exploration of immunogenic cell death and metal-organic frameworks represented recent areas of interest.

Conclusion: Through comprehensive analyses, an overview of current research trends and emerging areas of interest regarding the application of nanomaterials in ovarian cancer was illustrated. These findings offered valuable insights into the status and future directions of this dynamic field.

1 Introduction

Based on global estimates, approximately 314,000 cases of ovarian cancer (OC) are diagnosed annually, with around 207,000 cases of death each year ( Sung et al., 2021 ). OC is the primary cause of death among gynecologic cancers in the United States and ranks as the fifth most prevalent cause of cancer-related mortality in women ( Armstrong et al., 2021 ). The predominant challenges in managing OC lie in the advanced stage of the disease in initial diagnosis and the lack of effective corresponding therapeutic strategies ( Armstrong et al., 2021 ; Khan et al., 2021 ). Despite the utilization of various treatment schemes, such as combining biological agents with chemotherapies to impede tumor growth and minimize recurrence, the limited bioavailability of the drugs and their non-specific activation yield diminish the therapeutic efficacy and cause severe side effects to patients ( Lustberg et al., 2023 ). Consequently, there is an urgent necessity for innovative and efficient methods to diagnose and treat OC.

The development of nanotechnology provides a groundbreaking platform for novel material-based diagnosis and imaging of diseases with enhanced efficacy and properties, due to their distinct characteristics including adjustable size, strong affinity, stability, labeling function, thermal properties, and internalization capacity ( Rajitha et al., 2021 ). The integration of nanotechnology and pharmaceutical sciences has triggered a revolution in the medical domain. Numerous nanomaterials have been approved by the United States Food and Drug Administration (FDA) for the application in anticancer medications and diagnostic agents, and numerous clinical trials have been conducted to examine their potentials ( Nirmala et al., 2023 ).

Nanotechnology thus provides novel molecular agents that could enable OC diagnosis at initial stages and allow continuous monitoring during treatment ( Rajitha et al., 2021 ). By serving as contrast agents, molecular imaging agents and intraoperative aids, novel nanomaterials improve traditional clinical methods by recognizing OC early and precisely positioning it ( Henderson et al., 2021 ). For instance, Williams et al. reported a optically responsive carbon nanotube to detect the OC biomarker HE4 in vivo ( Williams et al., 2018 ). Pu T et al. developed nanoparticles with near-infrared-II fluorescence (NIR-II NPs) can accurately detect early orthotopic and advanced-stage metastatic OC in mice models ( Pu et al., 2023 ). Additionally, the utilization of nanoparticles (NPs) can also facilitate localized drug delivery, enhance drug retention, and minimize systemic toxicity when treating OC ( Bhattacharya et al., 2022 ; Zhang et al., 2023 ). Examples of NP formulations that have received FDA approval for the treatment of OC include Doxil ® , which is a liposomal formulation of doxorubicin and Abraxane ® , which is a human serum albumin nanoaggregate of paclitaxel ( Barenholz, 2012 ; Li et al., 2020 ; National Comprehensive Cancer Network, 2023 ).

Nevertheless, most of the nanomaterial products in nanomedicine are still in the stage of in vitro cell culture or in vivo animal experiments. There are several possible reasons why nanostructures have not improved clinical practice in OC as expected. Regulatory issues, safety concerns, nanomedicines’ physicochemical characteristics and manufacturing problems may account for this ( Zhang et al., 2023 ). Consequently, it is promising to use nanomaterials in cancer diagnosis and treatment, but many challenges must be overcome before they can be used clinically.

Bibliometric analysis is a statistical approach that utilizes public literature databases to conduct quantitative and qualitative evaluation on publications of interest, by which the research trends and hotpots within a specific field can be concluded. Recently, bibliometrics has been employed in the investigation of nanomaterials ( Bhandari et al., 2022 ; Zhao et al., 2022 ; Han et al., 2023 ). However, there is a dearth of bibliometric analysis regarding the utilization of nanomaterials in the context of OC. Therefore, this study utilized a quantitative methodology to illustrate the current situation of nanomaterials applied in OC treatment. Therefore, such quantitative methodology was utilized in this study in order to illustrate the current situation of nanomaterials applied in OC treatment. In this study, based on the Web of Science Core Collection (WOSCC) database, we used software such as VOSviewer, CiteSpace, and Pajek to conduct bibliometric and visual analysis on the research trends of countries/regions, institutions, authors, publications, citations, and keywords in the nanomaterials and OC field. This analysis helped identify research hotspots and provides suggestions for future research directions.

2.1 Data acquisition and filtration

To conduct data retrieval, we utilized the WOSCC database on 31 July 2023. The employed search formula was TS=(NANO*) AND TS=((“Ovarian Cancer*”) OR (“Ovarian Carcinoma”) OR (“Ovarian Neoplasm*”) OR (“Cancer of Ovary”) OR (“Cancer of the Ovary”)). The inclusion of the term “nano*” allowed the search to encompass all the terms beginning with “nano”, such as nanoparticles, nanomaterials, nanocomposites, nanocarriers, nanotechnology, and so on. The timeframe of the search spanned from 2003 to 2023, constituting a 20-year period. During the initial screening stage, only articles were included, while the irrelevant documents such as reviews, meeting abstracts, biographical-items, editorial materials, early access articles, letters, book chapters, proceeding papers, corrections, news items, and retracted papers were excluded. Furthermore, in order to refine our analysis, articles with reported contents unrelated to nanomaterials in the context of OC were manually excluded ( Figure 1 ).

FIGURE 1 . Flowchart of the literature screening process.

2.2 Data analysis

In our present investigation, VOSviewer (v1.6.18), CiteSpace (v6.1.6), Pajek (v5.16), Scimago Graphica (v1.0.35), and R-bibliometrix (v4.1.0) were applied to perform bibliometric and visual analyses. VOSviewer was mainly responsible for generating visual graphs and examining the countries, institutions, and authors with the most prolific collaborations, as well as the most frequently cited journals and cooccurring keywords. Meanwhile, CiteSpace was employed to construct a timeline graph and identify the bursts of keyword terms. Each dot on the visual graphs corresponds to a country, institution, author, or journal, and these dots were grouped based on their collaborative efforts. The size of the dot was dependent on the number of publications. Link strength (LS) was the thickness of the line connecting the nodes and represented the strength of cooperation between them, and total link strength (TLS) reflected the overall level of cooperation. In the keyword analysis, several insignificant keywords were excluded, and those with similar meanings were merged to gain a better perspective.

3.1 Analysis of general trend

In this study, a total of 2,426 related documents were identified and met the inclusion criteria, and the annual scientific productions showed a general ascending trend, indicating that attention to the field of OC and nanomaterials increased ( Figure 2 ).

FIGURE 2 . Trends in the volume of publications per year of nanomaterials in ovarian cancer.

3.2 Analysis of countries/regions

The coauthorship network visualization map of countries is shown in Figures 3A,B . A total of 72 countries/regions were presented. The United States exhibited the strongest international collaboration network (TLS = 436), which had the closest cooperation with China (LS = 134). Next, the number of publications was analyzed, revealing that China had the highest publication count (907, 37.39%), followed by the United States (826, 34.04%), and India (138, 5.69%).

FIGURE 3 . (A, B) The coauthorship network map of countries.

3.3 Analysis of institutions

From 2003 to 2022, a total of 2,438 institutions conducted studies in this field. The top three institutions were the Chinese Academy of Sciences (85 publications), Sichuan University (75 publications), and The University of Texas MD Anderson Cancer Center (62 publications). Institutions that had at least 10 publications were included in the analysis of collaborative networks which were visualized by VOSviewer. The clusters were arranged in different colors based on the frequency of collaboration between institutions ( Figure 4 ). The Chinese Academy of Sciences had the largest node (TLS = 92), indicating the highest level of collaboration with other institutions. The strongest connection was between the Chinese Academy of Sciences and the University of Chinese Academy of Sciences (LS = 32), which was represented by the thickest line. Figure 5 depicted the publications of the top 10 institutions with the most significant citation bursts, as indicated by the red bars. The publications of the Egyptian Knowledge Bank (EKB) and Islamic Azad University experienced a sharp increase from 2021 to 2023, with a burst intensity of 7.51 and 5.96, suggesting an increasing focus on the researches related to OC and nanomaterials during the past 3 years.

FIGURE 4 . The coauthorship network map of institutions.

FIGURE 5 . Top 10 institutions with the strongest citation bursts.

3.4 Analysis of authors

The author collaboration network map was presented in Figure 6 . A total of 13,140 authors have published relevant papers, with Anil K. Sood being the most influential author with 38 publications, followed by Gabriel Lopez-Berestein and Nicole F. Steinmetz. Anil K. Sood gained the highest number of collaborative relationships with other authors. Anil K. Sood and Gabriel Lopez-Berestein from the University of Texas MD Anderson Cancer Center in the United States possessed the closest collaboration. Figure 7 illustrated the citation bursts of the top ten authors, with the time interval and duration of the bursts marked in blue and red, respectively. Steinmetz, Nicole F from the University of California in the United States, as well as Xiao Haihua from the Chinese Academy of Science in China, have experienced a significant increase in their publication output in the past 3 years. This indicated a notable surge of their creativity in the nanomaterials and OC field.

FIGURE 6 . The coauthorship network map of authors.

FIGURE 7 . Top 10 authors with the strongest citation bursts.

3.5 Analysis of journals

Since 2000, a total of 558 journals have published articles related to nanomaterials and OC, as shown in Table 1 . Among those journals, ACS Nano has the highest impact factor (IF 2022 = 17.1), and 85% of the journals reached a JCR partition of Q1. We further refined our analysis by filtering out 118 journals with fewer than 5 relevant publications, resulting in 5 distinct clusters as presented in Figure 8 . Larger nodes in the figure indicated a greater number of relevant publications, while the connecting lines between nodes represented cross-citation relationships between two journals. It was notable that the journals publishing research on nanomaterials in the field of OC demonstrated an active citation relationship.

TABLE 1 . Top 10 journals in terms of the number of published papers.

FIGURE 8 . The cocitation network map of journals.

Figure 9 illustrated the dual-map overlay of journals contributing to publications in the field of nanomaterials and OC from 2003 to 2023. The left side represented the citing journals, while the right side represented the cited journals. The colored line paths indicated the citation relationships. The analysis revealed that the research primarily focused on journals in the fields of physics, materials, chemistry, molecular biology, immunology, medicine, and clinical studies. The cited journals were predominantly from the fields of molecular biology, genetics, chemistry, materials, and physics. This interdisciplinary network and collaboration actively reflects current trends in multiple fields, especially at the forefront of nanomaterials and medicine.

FIGURE 9 . The dual-map overlay of journals contributed to publications.

3.6 Analysis of co-cited references

Table 2 presented the top 10 co-cited publications related to nanomaterials and OC. The visualization of the co-cited publications was realized by CiteSpace software, with larger labels assigned to authors based on the number of citations ( Figure 10A ). It was noteworthy that the publication by Professor Siegel RL from the United States, which focused on the annual estimates and the latest data on cancer incidence, mortality, and survival in the United States in 2018, received the highest citations, of 152 ( Siegel et al., 2019 ). This publication was highly valuable for epidemiological studies since it provided the annual estimates of new cancer cases and deaths in the United States, along with the most recent data on population-based cancer incidence. Among the top 10 co-citations, the journal “CA: A Cancer Journal for Clinicians” holds the highest impact factor (IF 2022 = 254.7), followed by “Nature Reviews Cancer” (IF 2022 = 78.5). Furthermore, we utilized CiteSpace to identify the top 20 references that experienced a strong citation burst. A citation burst refers to references that have garnered substantial attention from other studies over a specific time period. Figure 10B illustrated that, since 2003, the strongest citation burst originated from the paper by Torre et al. ( Torre et al., 2018 )in 2018, followed by the article by Sung et al. ( Sung et al., 2021 ) on CA-CANCER J CLIN in 2021 and the article by Lheureux et al. ( Lheureux et al., 2019 ) on CA-CANCER J CLIN in 2019.

TABLE 2 . Top 10 cited publications.

FIGURE 10 . (A) Labels clustering of co-cited literature and (B) the top 20 references with the strongest citation bursts.

3.7 Analysis of keywords

Keyword co-occurrence analysis was conducted to identify popular research topics. Supplementary Figure S11A,B showed the network and overlay visualization maps of co-occurring keywords. The top 10 frequent keywords were OC, drug delivery, NPs, paclitaxel, cisplatin, doxorubicin, folic acid, apoptosis, chemotherapy, and nanomedicine. These keywords represented the key research areas within the field of nanomaterials and OC. The cluster analysis of the network map accurately reflected the knowledge structure of the research fields. By using VOSviewer software, we conducted a co-occurrence clustering analysis and visualization of keywords in the literature. A total of 132 out of 4,842 keywords were analyzed to achieve a minimum occurrence frequency of 7. Among these, the top 10 frequent keywords were OC, drug-delivery, NPs, paclitaxel, cisplatin, doxorubicin, cancer, folic acid, apoptosis, and chemotherapy. In Supplementary Figure S11A , the network map displayed 6 distinct clusters which were represented by different colors. The largest cluster marked in red was focused on the NP-based diagnosis and treatments, with prominent keywords such as “CA125”, “biomarkers”, “biosensor”, and “gene therapy”. The second largest cluster marked in green was mainly associated with nanotechnology, and keywords like “liposomes”, “nanocarriers”, “gene delivery”, and “self-assembly” were included. The blue marker, representing the third largest cluster, committed to drug delivery and loading agents, with keywords like “paclitaxel”, “cisplatin”, “doxorubicin”, and “siRNA” being central to this cluster. The yellow cluster was related to the targeting and imaging, with significant keywords such as “folic acid”, “EGFR”, “MRI”, and “magnetic NPs”. The purple cluster which was focused on targeting and therapy was characterized with keywords such as “cancer stem cell”, “ph-sensitive”, “photodynamic therapy”, and “photothermal therapy” being prominent. Lastly, the light blue cluster explored the anticancer mechanisms with frequent keywords such as “apoptosis”, “cytotoxicity”, “reactive oxygen species”, and “autophagy”.

The trend topic analysis was an important mapping tool that helped to portray the seed of trend integration rooted in the previous stream (Zhao et al., 2022). Supplementary Figure S11B , terms marked in purple indicate that their average year of publication was 2015 or earlier, while those marked in bright yellow appeared after 2019. Keywords such as “proteomics” and “nanoemulsion” were the main topics during the early stage. The keywords “immunogenic cell death” and “metal-organic framework” appeared relatively late in the study period.

In addition, we presented a visualization of the keyword evolution over time using CiteSpace ( Figure 11C ). Before 2010, the main hot research keywords were OC and drug delivery. As of 2023, OC, cell viability, and tumor targeting continue to be hot topics. Another important indicator of the study frontiers and hotspots over time was the strength of the keyword bursts ( Figure 11D ). Among the top 10 keywords with the strongest citation bursts, gold NPs had the highest burst strength in the last 3 years, suggesting that they are still popular research subjects.

FIGURE 11 . The network (A) , overlay (B) , and timeline (C) map of keyword co-occurrence. (D) the top 10 keywords with the strongest citation bursts.

4 Discussion

To our knowledge, for the first time this study conducted a comprehensive bibliometric analysis on the application of nanomaterials in OC between 2003 and 2023, which provided an overview of the global research landscape in this field, identified the research hotspots, and made predictions about future trends. According to the results, the research in this area has been developing rapidly over the past 2 decades.

Notably, China and the United States have emerged as the main contributors in this field. China has the highest number of publications, while the United States achieves the highest citation frequency and has the most extensive collaborations with other countries or regions. Among the top institutions in publication output, the Chinese Academy of Sciences stands out as the most productive institution in the collaborative network, with the highest overall link strength. In terms of publication output, The International Journal of Nanomedicine ranks as the top in this field. According to the authors’ viewpoint, KSood, Anil K turn to be the most influential authors, closely followed by Lopez-Berestein Gabriel, who are both affiliated with the University of Texas MD Anderson Cancer Center in the United States. Notably, Steinmetz, Nicole F from the University of California in the United States and Xiao, Haihua from the Chinese Academy of Science have made significant contributions with extensive publication records in the past 3 years. These noteworthy achievements could be attributed to the support provided by institutions in both China and the United States, including their policies and financial funding, which have fostered extensive and in-depth researches in this particular field.

The keyword analysis revealed that the most frequently recurring keywords were associated with drug delivery, emphasizing its status as an extensively studied subfield. Notably, recent hot spots in the research keywords included “immunogenic cell death” and “metal-organic framework,” indicating the latest areas of interest in this field. Among these hot spots, the researches on gold NPs have obtained remarkable burst strength over the last 3 years, holding promising potentials in OC diagnosis, treatment, and drug delivery, both in vivo and in vitros. Furthermore, recent studies have shed light on the significant role of nanomaterials in cancer immune regulation. With proper optimization in the structure and functions, nanoparticles can be utilized to directly reverse the immune status of primary tumors, stimulate the potential of peripheral immune cells, prevent the formation of pre-metastatic niches, and suppress tumor recurrence through postoperative immunotherapy ( Zhang et al., 2021 ; Li et al., 2022 ). Therefore, the combination of advanced immunotherapy and novel nanomaterials is burgeoning as a reliable scheme for the treatment of refractory and metastatic malignancies in the future.

The unique physical and chemical properties of nanomaterials facilitate a wide rage of applications, especially in the field of cancer therapy. OC is a highly fatal gynecological malignancy worldwide, which is known for its significant morbidity and mortality. Conventional chemotherapeutic drugs often fail to achieve satisfying effects in treating OC due to drug resistance. However, the auxiliary application of nanomaterials can enhance drug accumulation in tumors, reduce off-target toxicity, prevent rapid drug clearance after systemic delivery, and improve the pharmacokinetics of the drug, ultimately leading to higher therapeutic efficiency ( Baranello et al., 2014 ; Chen et al., 2021 ). Nano-technique is considered as an effective approach to address the poor aqueous solubility of hydrophobic drugs. For example, exosomal and liposomal nano-carriers for mangiferin and curcumin exhibited increased cellular uptake and controlled release ( Alharbi et al., 2024 ). Nanocarriers have also been used to specifically target to tumors, such as the tumor-targeted probes for Follicle-stimulating hormone ( Liu et al., 2024 ). Furthermore, multifunctional nanoparticles (DDP-Ola@HR) which were loaded with both DDP and Olaparib and modified with heparin, have shown effectiveness in inhibiting the growth and metastasis of DDP-resistant OC( Liang et al., 2023 ). However, there are challenges that need to be addressed. Long-term toxicity and side effects of nanomaterials require further study, since the verification of bio-safety on the monthly bases is too short to fully understand. In addition, the complex manufacturing process of nanomedicines can result in inconsistency between different batches, and for the quality control of laboratory manufacture, there is still a long way to reach the criteria of clinical application.

Despite these challenges, nanomaterials hold the promise in various treatment approaches for OC, including phototherapy, chemotherapy, targeted therapy, and combination therapy. The limitations of chemotherapeutic drugs, such as poor water solubility, adverse side effects, and multidrug resistance, can be removed with the use of nanomaterials. In recent years, there have been developments in the use of MO based NPs to address solubility issues of hydrophobic drugs. The drug was loaded in nanocarriers through encapsulation, with a high drug loading rate up to 10 wt% ( Zhai et al., 2018 ). Another approach focused on the use of nano-micelles to deliver anti-tumor drugs such as betulinic acid and paclitaxel, which has shown promising therapeutic efficacy in tumors with multidrug resistance ( Qu et al., 2023 ). To overcome the limitations of monotherapy, a multi-mode nanoplatform called Fe-Dox/PVP was designed to combine chemotherapy, ferroptosis, and mild photothermal therapy. This nanoplatform exhibited significant anticancer effects both in vitro and in vivo ( Dai et al., 2023 ). Overall, more researches are needed in order to fully address the problem of OC and make the most of the advantages nanomaterials.

The application of nanotechnology in treating OC has experienced significant growth over the past 2 decades. A number of clinical trials have been conducted to assess the effectiveness of nanomedicines in treating relapsed or refractory OC. These studies have utilized nanocarriers to load various drugs, including doxorubicin (NCT0148937), paclitaxel (NCT02125662), cisplatin (NCT02790858), oxaliplatin (NCT02565349), carboplatin (NCT03071672), and siRNA (NCT02541521). The results of these trials verified the potential and feasibility of nanomedicines in treating OC. Notably, the FDA has approved Doxil ® (liposomal doxorubicin), and Abraxane ® (albumin-bound paclitaxel) as two important chemotherapy options for the clinical treatment of OC ( Barenholz, 2012 ; Li et al., 2020 ; National Comprehensive Cancer Network, 2023 ). In recent years, researchers have been drawing growing attention on nanomedicine carrier design, precisely targeted drugs, and multimodal combined multimodal therapy ( Li et al., 2020 ). Overall, improvements in clinical research on OC therapy have achieved, although further research and exploration are still necessary to develop strategies with better therapeutic effects and higher bio-safety.

It is undeniable that there are limitations in this study. The literature search was limited to the WoSCC database, which may have resulted in an incomplete conclusion. nevertheless, the WoSCC database is widely recognized as one of the most comprehensive sources for bibliometric analysis. Additionally, only studies published in English were included.

In conclusion, this study utilized various statistical software programs to conduct a bibliometric analysis on nanomaterials in the diagnosis and treatment of OC. The advantages and challenges faced by nanomaterials in this field were discussed. Nanomaterials have the potential to be a powerful tool in the diagnosis and treatment of OC. This study provides valuable insights into the recent developments and trends in the use of nanomaterials for treating OC, offering researchers a conclusive and convenient port to learn about the current circumstances in this field National Comprehensive Cancer Network, 2023 .

Data availability statement

The original contributions presented in the study are included in the article/ Supplementary Material , further inquiries can be directed to the corresponding authors.

Author contributions

WW: Writing–review and editing, Writing–original draft. JW: Writing–original draft. DF: Writing–review and editing. BL: Writing–review and editing.

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Capital’s Funds for Health Improvement and Research (No. 2022-2-406) and the Funds of the China-Japan Friendship Hospital (No. 2017-RC-4).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2024.1344855/full#supplementary-material

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Keywords: bibliometric analysis, ovarian cancer, nanomaterial, research trend, visualization

Citation: Wang W, Wei J, Feng D and Ling B (2024) Current trends and emerging patterns in the application of nanomaterials for ovarian cancer research: a bibliometric analysis. Front. Pharmacol. 15:1344855. doi: 10.3389/fphar.2024.1344855

Received: 26 November 2023; Accepted: 22 February 2024; Published: 08 March 2024.

Reviewed by:

Copyright © 2024 Wang, Wei, Feng and Ling. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Dingqing Feng, [email protected] Bin Ling, [email protected]

† These authors have contributed equally to this work

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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Nanotechnology: A Revolution in Modern Industry

Shiza malik.

1 Bridging Health Foundation, Rawalpindi 46000, Pakistan

Khalid Muhammad

2 Department of Biology, College of Science, UAE University, Al Ain 15551, United Arab Emirates

Yasir Waheed

3 Office of Research, Innovation, and Commercialization (ORIC), Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad 44000, Pakistan

4 Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos 1401, Lebanon

Associated Data

Not applicable.

Nanotechnology, contrary to its name, has massively revolutionized industries around the world. This paper predominantly deals with data regarding the applications of nanotechnology in the modernization of several industries. A comprehensive research strategy is adopted to incorporate the latest data driven from major science platforms. Resultantly, a broad-spectrum overview is presented which comprises the diverse applications of nanotechnology in modern industries. This study reveals that nanotechnology is not limited to research labs or small-scale manufacturing units of nanomedicine, but instead has taken a major share in different industries. Companies around the world are now trying to make their innovations more efficient in terms of structuring, working, and designing outlook and productivity by taking advantage of nanotechnology. From small-scale manufacturing and processing units such as those in agriculture, food, and medicine industries to larger-scale production units such as those operating in industries of automobiles, civil engineering, and environmental management, nanotechnology has manifested the modernization of almost every industrial domain on a global scale. With pronounced cooperation among researchers, industrialists, scientists, technologists, environmentalists, and educationists, the more sustainable development of nano-based industries can be predicted in the future.

1. Introduction

Nanotechnology has slowly yet deeply taken over different industries worldwide. This rapid pace of technological revolution can especially be seen in the developed world, where nano-scale markets have taken over rapidly in the past decade. Nanotechnology is not a new concept since it has now become a general-purpose technology. Four generations of nanomaterials have emerged on the surface and are used in interdisciplinary scientific fields; these are active and passive nanoassemblies, general nanosystems, and small-scale molecular nanosystems [ 1 ].

This rapid development of nanoscience is proof that, soon, nano-scale manufacturing will be incorporated into almost every domain of science and technology. This review article will cover the recent advanced applications of nanotechnology in different industries, mainly agriculture, food, cosmetics, medicine, healthcare, automotive, oil and gas industries, chemical, and mechanical industries [ 2 , 3 ]. Moreover, a brief glimpse of the drawbacks of nanotechnology will be highlighted for each industry to help the scientific community become aware of the ills and benefits of nanotechnology side by side. Nanotechnology is a process that combines the basic attributes of biological, physical, and chemical sciences. These processes occur at the minute scale of nanometers. Physically, the size is reduced; chemically, new bonds and chemical properties are governed; and biological actions are produced at the nano scale, such as drug bonding and delivery at particular sites [ 4 , 5 ].

Nanotechnology provides a link between classical and quantum mechanics in a gray area called a mesoscopic system. This mesoscopic system is being used to manufacture nanoassemblies of nature such as agricultural products, nanomedicine, and nanotools for treatment and diagnostic purposes in the medical industry [ 6 ]. Diseases that were previously untreatable are now being curtailed via nano-based medications and diagnostic kits. This technology has greatly affected bulk industrial manufacturing and production as well. Instead of manufacturing materials by cutting down on massive amounts of material, nanotechnology uses the reverse engineering principle, which operates in nature. It allows the manufacturing of products at the nano scale, such as atoms, and then develops products to work at a deeper scale [ 7 ].

Worldwide, millions and billions of dollars and euros are being spent in nanotechnology to utilize the great potential of this new science, especially in the developed world in Europe, China, and America [ 8 ]. However, developing nations are still lagging behind as they are not even able to meet the industrial progression of the previous decade [ 9 ]. This lag is mainly because these countries are still fighting economically, and they need some time to walk down the road of nanotechnology. However, it is pertinent to say that both the developed and developing world’s scientific communities agree that nanotechnology will be the next step in technological generation [ 10 ]. This will make further industrial upgrading and investment in the field of nanotechnology indispensable in the coming years.

With advances in science and technology, the scientific community adopts technologies and products that are relatively cheap, safe, and cleaner than previous technologies. Moreover, they are concerned about the financial standing of technologies, as natural resources in the world are shrinking excessively [ 11 ]. Nanotechnology thus provides a gateway to this problem. This technology is clear, cleaner, and more affordable compared to previous mass bulking and heavy machinery. Moreover, nanotechnology holds the potential to be implemented in every aspect of life. This will mainly include nanomaterial sciences, nanoelectronics, and nanomedicine, being inculcated in all dimensions of chemistry and the physical and biological world [ 12 ]. Thus, it is not wrong to predict that nanotechnology will become a compulsory field of study for future generations [ 13 ]. This review inculcates the basic applications of nanotechnology in vital industries worldwide and their implications for future industrial progress [ 14 ].

2. Nanotechnology Applications

2.1. applications of nanotechnology in different industries.

After thorough and careful analyses, a wide range of industries—in which nanotechnology is producing remarkable applications—have been studied, reviewed, and selected to be made part of this review. It should be notified that multiple subcategories of industrial links may be discussed under one heading to elaborate upon the wide-scale applications of nanotechnology in different industries. A graphical abstract at the beginning of this article indicates the different industries in which nanotechnology is imparting remarkable implications, details of which are briefly discussed under different headings in the next session.

2.2. Nanotechnology and Computer Industry

Nanotechnology has taken its origins from microengineering concepts in physics and material sciences [ 15 ]. Nanoscaling is not a new concept in the computer industry, as technologists and technicians have been working for a long time to design such modified forms of computer-based technologies that require minimum space for the most efficient work. Resultantly, the usage of nanotubes instead of silicon chips is being increasingly experimented upon in computer devices. Feynman and Drexler’s work has greatly inspired computer scientists to design revolutionary nanocomputers from which wide-scale advantages could be attained [ 13 ]. A few years ago, it was an unimaginable to consider laptops, mobiles, and other handy gadgets as thin as we have today, and it is impossible for even the common man to think that with the passage of time, more advanced, sophisticated, and lighter computer devices will be commonly used. Nanotechnology holds the potential to make this possible [ 16 ].

Energy-efficient, sustainable, and urbanized technologies have been emerging since the beginning of the 21st century. The improvement via nanotechnology in information and communication technology (ICT) is noteworthy in terms of the improvements achieved in interconnected communities, economic competitiveness, environmental stability during demographic shifts, and global development [ 17 ]. The major implications of renewable technology incorporate the roles of ICT and nanotechnology as enablers of environmental sustainability. The traditional methods of product resizing, re-functioning, and enhanced computational capabilities, due to their expensiveness and complicated manufacturing traits, have slowly been replaced by nanotechnological renovations. Novel technologies such as smart sensors logic elements, nanochips, memory storage nanodevices, optoelectronics, quantum computing, and lab-on-a-chip technologies are important in this regard [ 18 ].

Both private and public spending are increasing in the field of nanocomputing. The growth of marketing and industrialization in the biotechnology and computer industries are running in parallel, and their expected growth rates for the coming years are far higher. Researchers and technologists believe that by linking the advanced field of nanotechnology and informatics and computational industries, various problems in human society such as basic need fulfillment can be easily accomplished in line with the establishment of sustainable goals by the end of this decade [ 19 ]. The fourth industrial revolution is based upon the supporting pillars derived from hyperphysical systems including artificial intelligence, machine learning, the internet of things, robots, drones, cloud computing, fast internet technologies (5G and 6G), 3D printing, and block chain technologies [ 20 ].

Most of these technologies have a set basis in computing, nanotechnology, biotechnology, material science renovations, and satellite technologies. Nanotechnology offers useful alterations in the physiochemical, mechanical, magnetic, electrical, and optical properties of computing materials which enable innovative and newer products [ 21 ]. Thus, nanotechnology is providing a pathway for another broad-spectrum revolution in the field of automotive, aerospace, renewable energy, information technology, bioinformatics, and environmental management, all of which have root origins from nanotechnological improvements in computers. Sensors involved in software and data algorithms employ nanomaterials to induce greater sensitivity and processabilities with minimal margin-to-machine errors [ 22 ]. Nanomaterials provide better characteristics and robustness to sensor technologies which mean they are chemically inert, corrosion-resistant, and have greater tolerance profiles toward temperature and alkalinity [ 22 ].

Moreover, the use of semiconductor nanomaterials in the field of quantum computing has increased overall processing speeds with better accuracy and transmissibility. These technologies offer the creation of different components and communication protocols at the nano level, which is often called the internet of nano things [ 23 ]. This area is still in a continuous development and improvement phase with the potential for telecommunication, industrial, and medical applications. This field has taken its origin from the internet of things, which is a hyperphysical world of sensors, software, and other related technologies which allow broad-scale communication via internet operating devices [ 17 ]. The applications of these technologies range from being on the simple home scale to being on the complex industrial scale. The internet of things is mainly capable of gathering and distributing large-scale data via internet-based equipment and modern gadgets. In short, the internet of nano things is applicable to software, hardware, and network connection which could be used for data manipulation, collection, and sharing across the globe [ 24 ].

Another application of nanotechnology in the computer and information industry comes in the form of artificial intelligence, machine learning, and big data platforms which have set the basis for the fourth industrial revolution. Vast amounts of raw data are collected through interconnected robotic devices, sensors, and machines which have properties of nanomaterials [ 18 ]. After wide-scale data gathering, the next step is the amalgamation of the internet of things and the internet of people to prepare a greater analysis, understanding, and utilization of the gathered information for human benefit [ 4 ]. Such data complications can be easily understood through the use of big data in the medical industry, in which epidemiological data provide benefits for disease management [ 2 ]. Yet another example is the applications in business, where sales and retail-related data help to elucidate the target markets, sales industry, and consumer behavioral inferences for greater market consumption patterns [ 19 ].

Similarly, an important dimension of nanotechnology and computer combination comes in the form of drone and robotics technology. These technologies have a rising number of applications in maintenance, inspections, transportation, deliverability, and data inspection [ 25 ]. Drones, robots, and the internet of things are being perfectly amalgamated with the industrial sector to achieve greater goals. Drones tend to be more mobile but rely more on human control as compared to robots, which are less mobile but have larger potential for self-operation [ 26 ]. However, now, more mobile drones with better autonomous profiles are being developed to help out in the domain of manufacturing industries. These devices intensify and increase the pace of automation and precision in industries along with providing the benefits of lower costs and fewer errors [ 24 ]. The integrated fields of robotics, the internet of things, and nanotechnology are often called the internet of robotics and nano things. This field of nanorobotics is increasing the flexibility and dexterity in manufacturing processes compared to traditional robotics [ 25 ].

Drones, on the contrary, help to manage tasks that are otherwise difficult or dangerous to be managed by humans, such as working from a far distance or in dangerous regions. Nanosensors help to equip drones with the qualities of improved detection and sensation more precisely than previous sensor technologies [ 21 , 27 ]. Moreover, the over-potential of working hours, battery, and maintenance have also been improved with the operationalization of nano-based sensors in drone technology. These drones are inclusively used for various purposes such as maintaining operations, employing safety profiling, security surveys, and mapping areas [ 18 ]. However, limitations such as high speed, legal and ethical limitations, safety concerns, and greater automobility are some of the drawbacks of aerial and robotic drone technologies [ 26 ].

Three-dimensional printing is yet another important application of the nanocomputer industry, in which an integrated modus operandi works to help in production management [ 28 ]. Nanotechnology-based 3D printing offers the benefits of an autonomous, integrated, intelligent exchange network of information which enables wide-scale production benefits. These technologies have enabled a lesser need for industrial infrastructure, minimized post-processing operations, reduced waste material generation, and reduced need for human presence for overall industrial management [ 28 , 29 ]. Moreover, the benefits of 3D printing and similar technologies have potentially increased flexibility in terms of customized items, minimal environmental impacts, and sustainable practices with lower resource and energy consumption. The use of nano-scale and processed resins, metallic raw material, and thermoplastics along with other raw materials allow for customized properties of 3D printing technology [ 29 ].

The application of nanotechnology in computers cannot be distinguished from other industrial applications, because everything in modern industries is controlled by a systemic network in association with a network of computers and similar technologies. Thus, the fields of electronics, manufacturing, processing, and packaging, among several others, are interlinked with nanocomputer science [ 11 , 15 ]. Silicon tubes have had immense applications that revolutionized the industrial revolution in the 20th century; now, the industrial revolution is in yet another revolutionary phase based on nanostructures [ 16 ]. Silicon tubes have been slowly replaced with nanotubes, which are allowing a great deal of improvement and efficiency in computing technology. Similarly, lab-on-a-chip technology and memory chips are being formulated at nano scales to lessen the storage space but increase the storage volume within a small, flexible, and easily workable chip in computers for their subsequent applications in multiple other industries.

Hundreds of nanotechnology computer-related products have been marketed in the last 20 years of the nanotechnological revolution [ 30 ]. Modern industries such as textiles, automotive, civil engineering, construction, solar technologies, environmental applications, medicine, transportation agriculture, and food processing, among others are largely reaping the benefits of nano-scale computer chips and other devices. In simple terms, everything out there in nanoindustrial applications has something to do with computer-based applications in the nanoindustry [ 31 , 32 , 33 ]. Thus, all the applications discussed in this review more or less originate from nanocomputers. These applications are enabling considerable improvement and positive reports within the industrial sector. Having said that, it is hoped that computer scientists will remain engaged and will keep on collaborating with scientists in other fields to further explore the opportunities associated with nanocomputer sciences.

2.3. Nanotechnology and Bioprocessing Industries

Scientific and engineering rigor is being carried out to the link fields of nanotechnology with contributions to the bioprocessing industry. Researchers are interested in how the basics of nanomaterials could be used for the high-quality manufacturing of food and other biomaterials [ 15 , 34 ]. Pathogenic identification, food monitoring, biosensor devices, and smart packaging materials, especially those that are reusable and biodegradable, and the nanoencapsulation of active food compounds are only a few nanotechnological applications which have been the prime focus of the research community in recent years. Eventually, societal acceptability and dealing with social, cultural, and ethical concerns will allow the successful delivery of nano-based bio-processed products into the common markets for public usage [ 20 , 35 ].

With the increasing population worldwide, food requirements are increasing in addition to the concerns regarding the production of safe, healthy, and recurring food options. Sensors and diagnostic devices will help improve the sensitivity in food quality monitoring [ 36 ]. Moreover, the fake industrial application of food products could be easily scanned out of a system with the application of nanotechnology which could control brand protection throughout bio-processing [ 6 ]. The power usage in food production might also be controlled after a total nanotechnological application in the food industry. The decrease in power consumption would ultimately be positive for the environment. This could directly bring in the interplay of environment, food, and nanotechnology and would help to reduce environmental concerns in future [ 37 ].

One of the important implications of nanotechnology in bioprocessing industries can be accustomed to fermentation processes; these technologies are under usage for greater industrial demand and improved biomolecule production at a very low cost, unlike traditional fermentation processes [ 35 ]. The successful implementation and integration of fermentation and nanotechnology have allowed the development of biocompatible, safe, and nontoxic substances and nanostructures with wide-scale application in the field of food, bioprocessing, and winemaking industries [ 38 ]. Another important application is in the food monitoring and food supply chain management, present in various subsectors such as production, storage, distribution, and toxicity management. Nanodevices and nanomaterials are incorporated into chemical and biological sensor technologies to improve overall analytical performance with regard to parameters such as response time, sensitivity, selectivity, accuracy, and reliability [ 39 ]. The conventional methods of food monitoring are slowly being replaced with modern nano-based materials such as nanowires, nanocomposites, nanotubes, nanorods, nanosheets, and other materials that function to immobilize and label components [ 40 ]. These methods are either electrochemically or optically managed. For food monitoring, several assays are proposed and implemented with their roots in nano-based technologies; they may include molecular and diagnostic assays, immunological assays, and electrochemical and optical assays such as surface-enhanced Raman scattering and colorimetry technologies [ 34 ]. Materials ranging from heavy materials to microorganisms, pesticides, allergens, and antibiotics are easily monitored during commercial processing and bioprocessing in industries.

Additionally, nanotechnology has presented marvelous transformations in bio-composting materials. With the rising demand for biodegradable composites worldwide to reduce the environmental impact and increase the efficiency of industrial output, there is an increasing need for sustainable technologies [ 41 ]. Nanocomposites are thus being formulated with valuable mechanical properties better than conventional polymers, thus establishing their applicability in industries. The improved properties include optical, mechanical, catalytic, electrochemical, and electrical ones [ 42 ]. These biodegradable polymers are not only used in bioprocessing industries to create food products with relevant benefits but are also being deployed in the biomedical field, therapeutic industries, biotechnology base tissue engineering field, packing, sensor industries, drug delivery technology, water remediation, food industries, and cosmetics industries as well [ 2 , 24 , 34 , 43 ]. These nanocomposites have outstanding characteristics of biocompatibility, lower toxicities, antimicrobial activity, thermal resistance, and overall improved biodegradation properties which make them worthy of applications in products [ 44 ]. However, it is still imperative to conduct wide-scale toxicity and safety profiling for these and other nanomaterials to ensure the safety requirements, customer satisfaction, and public benefit are met [ 44 ].

Moreover, the advancement of nanotechnology has also been conferred to the development of functional food items. The exposure and integration of nanotechnology and the food industry have resulted in larger quantities of sustainable, safer, and healthier food products for human consumption, which is a growing need for the rising population worldwide [ 45 ]. The overall positive impact of nanotechnology in food processing, manufacturing, packing, pathogenic detection, monitoring, and production profiles necessitates the wide-scale application of this technology in the food industry worldwide [ 4 , 41 ]. Recent research has shown how the delivery of bioactive compounds and essential ingredients is and can be improved by the application of nanomaterials (nanoencapsulation) in food products [ 46 ]. These technologies improve the protection performance and sensitivity of bioactive ingredients while preventing unnecessary interaction with other constituents of foods, thus establishing clear-cut improved bioactivity and solubility profiles of nanofoods, thereby improving human health benefits. However, it should be kept in mind that the safety regards of these food should be carefully regulated with safety profiling, as they directly interact with human bodies [ 47 ].

2.4. Nanotechnology and Agri-Industries

Agriculture is the backbone of the economies of various nations around the globe. It is a major contributing factor to the world economy in general and plays a critical role in population maintenance by providing nutritional needs to them. As global weather patterns are changing owing to the dramatic changes caused by global warming, it is accepted that agriculture will be greatly affected [ 48 ]. Under this scenario, it is always better to take proactive measures to make agricultural practices more secure and sustainable than before. Modern technology is thus being employed worldwide. Nanotechnology has also come to play an effective role in this interplay of sustainable technologies. It plays an important role during the production, processing, storing, packaging, and transport of agricultural industrial products [ 49 ].

Nanotechnology has introduced certain precision farming techniques to enhance plant nutrients’ absorbance, alongside better pathogenic detection against agricultural diseases. Fertilizers are being improved by the application of nanoclays and zeolites which play effective roles in soil nutrient broths and in the restoration soil fertility [ 49 ]. Modern concepts of smart seeds and seed banks are also programmed to germinate under favorable conditions for their survival; nanopolymeric mixtures are used for coating in these scenarios [ 50 ]. Herbicides, pesticides, fungicides, and insecticides are also being revolutionized through nanotechnology applications. It has also been considered to upgrade linked fields of poultry and animal husbandry via the application of nanotechnology in treatment and disinfection practices.

2.5. Nanotechnology and Food Industry

The applications of nanotechnology in the food industry are immense and include food manufacturing, packaging, safety measures, drug delivery to specific sites [ 51 ], smart diets, and other modern preservatives, as summarized in Figure 1 . Nanomaterials such as polymer/clay nanocomposites are used in packing materials due to their high barrier properties against environmental impacts [ 52 ]. Similarly, nanoparticle mixtures are used as antimicrobial agents to protect stored food products against rapid microbial decay, especially in canned products. Similarly, several nanosensor and nano-assembly-based assays are used for microbial detection processes in food storage and manufacturing industries [ 53 ].

Nanotechnology applications in food and interconnected industries.

Nanoassemblies hold the potential to detect small gasses and organic and inorganic residues alongside microscopic pathogenic entities [ 54 ]. It should, however, be kept in mind that most of these nanoparticles are not directly added to food species because of the risk of toxicity that may be attached to such metallic nanoparticles. Work is being carried out to predict the toxicity attached, so that in the future, these products’ market acceptability could be increased [ 55 ]. With this, it is pertinent to say that nanotechnology is rapidly taking steps into the food industry for packing, sensing, storage, and antimicrobial applications [ 56 ].

Nanotechnology is also revolutionizing the dairy industry worldwide [ 57 ]. An outline of potential applications of nanotechnology in the dairy industry may include: improved processing methods, improved food contact and mixing, better yields, the increased shelf life and safety of dairy-based products, improved packaging, and antimicrobial resistance [ 58 ]. Additionally, nanocarriers are increasingly applied to transfer biologically active substances, drugs, enhanced flavors, colors, odors, and other food characteristics to dairy products [ 59 ].

These compounds exhibit higher delivery, solubility, and absorption properties to their targeted system. However, the problem of public acceptability due to the fear of unknown or potential side effects associated with nano-based dairy and food products needs to be addressed for the wider-scale commercialization of these products [ 60 ].

2.5.1. Nanotechnology, Poultry and Meat Industry

The poultry industry is a big chunk of the food industry and contributes millions of dollars every year to food industries around the world. Various commercial food chains are running throughout the world, the bases of which start from healthy poultry industries. The incidence of widespread foodborne diseases that originate from poultry, milk, and meat farms is a great concern for the food industry. Nanobiotechnology is certainly playing a productive role in tackling food pathogens such as those which procreate from Salmonella and Campylobacter infections by allowing increased poultry consumption while maintaining the affordability and safety of manufactured chicken products [ 61 ]. Several nano-based tools and materials such as nano-enabled disinfectants, surface biocides, protective clothing, air and water filters, packaging materials, biosensors, and detective devices are being used to confirm the authenticity and traceability of poultry products [ 62 ]. Moreover, nano-based materials are used to reduce foodborne pathogens and spoilage organisms before the food becomes part of the supply chain [ 63 ].

2.5.2. Nanotechnology—Fruit and Vegetable Industry

As already described, nanotechnology has made its way far ahead in the food industry. The agricultural, medicinal, and fruit and vegetable industries cannot remain unaffected under this scenario. Scientists are trying to increase the shelf life of fresh organic products to fulfill the nutritional needs of a growing population. From horticulture to food processing, packaging, and pathogenic detection technology, nanotechnology plays a vital role in the safety and production of vegetables and fruits [ 64 ].

Conventional technologies are now being replaced with nanotechnology due to their benefits of cost-effectiveness, satisfactory results, and overall shelf life improvement compared to past practices. Although some risks may be attached, nanotechnology has not yet reported high-grade toxicity to organic fresh green products. These technologies serve the purpose of providing safe and sufficient food sources to customers while reducing postharvest wastage, which is a major concern in developing nations [ 55 ]. Nanopackaging provides the benefits of lower humidity, oxygen passage, and optimal water vapor transmission rates. Hence, in the longer run, the shelf life of such products is increased to the desired level using nanotechnology [ 65 ].

2.5.3. Nanotechnology and Winemaking Industry

The winemaking industry is a big commercial application of the food industry worldwide. The usage of nanotechnology is also expanding in this industry. Nanotechnology serves the purpose of sensing technology through employment as nanoelectronics, nanoelectrochemical, and biological, amperometric, or fluorimetric sensors. These nanomaterials help to analyze the wine components, including polyphenols, organic acids, biogenic amines, or sulfur dioxide, and ensure they are at appropriate levels during the production of wine and complete processing [ 66 ].

Efforts are being made to further improve sensing nanotechnology to increase the accuracy, selectivity, sensitivity, and rapid response rate for wine sampling, production, and treatment procedures [ 53 ]. Specific nanoassemblies that are used in winemaking industries include carbon nanorods, nanodots, nanotubes, and metallic nanoparticles such as gold, silver, zinc oxide, iron oxide, and other types of nanocomposites. Recent research studies have introduced the concept of electronic tongues, nanoliquid chromatography, mesoporous silica, and applications of magnetic nanoparticles in winemaking products [ 67 ]. An elaborative account of these nanomaterials is out of the scope of the present study; however, on a broader scale, it is not wrong to say that nanotechnology is successfully reaping in the field of enology.

2.6. Nanotechnology and Packaging Industries

The packaging industry is continuously under improvement since the issue of environmentalism has been raised around the globe. Several different concerns are linked to the packaging industry; primarily, packaging should provide food safety to deliver the best quality to the consumer end. In addition, packaging needs to be environmentally friendly to reduce the food-waste-related pollution concern and to make the industrial processes more sustainable. Trials are being carried out to reduce the burden by replacing non-biodegradable plastic packaging materials with eco-friendly organic biopolymer-based materials which are processed at the nano scale to incur the beneficial properties of nanotechnology [ 68 ].

The nanomanufacturing of packaging biomaterials has proven effective in food packaging industries, as nanomanufacturing not only contributes to increasing food safety and production but also tackles environmental issues [ 69 ]. Some examples of these packaging nanomaterials may include anticaking agents, nanoadditives, delivery systems for nutraceuticals, and many more. The nanocompositions of packing materials are formed by mixing nanofillers and biopolymers to enhance packaging’s functionality [ 70 ]. Nanomaterials with antimicrobial properties are preferred in these cases, and they are mixed with a polymer to prevent the contamination of the packaged material. It is important to mention here that this technology is not only limited to food packaging; instead, packaging nanotechnology is now also being introduced in certain other industries such as textile, leather, and cosmetic industries in which it is providing large benefits to those industries [ 64 ].

2.7. Nanotechnology and Construction Industry and Civil Engineering

Efficient construction is the new normal application for sustainable development. The incorporation of nanomaterials in the construction industry is increasing to further the sustainability concern [ 71 ]. Nanomaterials are added to act as binding agents in cement. These nanoparticles enhance the chemical and physical properties of strength, durability, and workability for the long-lasting potential of the construction industry. Materials such as silicon dioxide which were previously also in use are now manufactured at the nano scale [ 71 ]. These nanostructures along with polymeric additives increase the density and stability of construction suspension [ 72 ]. The aspect of sustainable development is being applied to the manufacture of modern technologies coupled with beneficial applications of nanotechnology. This concept has produced novel isolative and smart window technologies which have driven roots in nanoengineering, such as vacuum insulation panels (VIPs) and phase change materials (PCMs), which provide thermal insulation effects and thus save energy and improve indoor air quality in homes [ 73 ].

A few of the unique properties of nanomaterials in construction include light structure, strengthened structural composition, low maintenance requirements, resistant coatings, improved pipe and bridge joining materials, improved cementitious materials, extensive fire resistance, sound absorption, and insulation properties, as well as the enhanced reflectivity of glass surfaces [ 74 ]. As elaborated under the heading of civil engineering applications, concrete’s properties are the most commonly discussed and widely changing in the construction industry because of concrete’s minute structure, which can be easily converted to the nano scale [ 75 ]. More specifically, the combination of nano-SiO 2 in cement could improve its performance in terms of compressiveness, large volumes with increased compressiveness, improved pore size distribution, and texture strength [ 76 ].

Moreover, some studies are also being carried out to improve the cracking properties of concrete by the application of microencapsulated healing polymers, which reduce the cracking properties of cement [ 77 ]. Moreover, some other construction materials, such as steel, are undergoing research to change their structural composites through nano-scale manufacturing. This nanoscaling improves steel’s properties such as improved corrosion resistance, increased weldability, the ease of handling for designing building materials, and construction work [ 78 ]. Additionally, coating materials have been improved by being manufactured at the nano scale. This has led to different improved coating properties such as functional improvement; anticorrosive action; high-temperature, fire, scratch, and abrasion resistance; antibacterial and antifouling self-healing capabilities; and self-assembly, among other useful applications [ 79 ].

Nanotechnology improves the compressive flexural properties of cement and reduces its porosity, making it absorb less water compared to traditional cementation preparations. This is because of the high surface-to-volume ratio of nanosized particles. Such an approach helps in reducing the amount of cement in concrete, making it more cost-effective, more strengthening, and eco-friendly, known as ‘green concrete’. Besides concrete, the revolutionary characteristics of nanotechnology are now also being adopted in other construction materials such as steel, glass, paper, wood, and multiple other engineering materials to upgrade the construction industry [ 80 ].

Similarly, carbon nanotubes, nanorods, and nanofibers are rapidly replacing steel constructions. These nanostructures along with nanoclay formations increase the mechanical properties and thus have paved the way for a new branch of civil engineering in terms of nanoengineering [ 80 ]. Apart from cement formulations, nanoparticles are included in repair mortars and concrete with healing properties that help in crack recovery in buildings. Furthermore, nanostructures, titanium dioxide, zinc, and other metallic oxides are being employed for the production of photocatalytic products with antipathogenic, self-cleaning, and water- and germ-repellent built-in technologies [ 33 ]. Similarly, quantum dot technologies are progressively employed for solar energy generation (a concept discussed later). These photovoltaic cells contribute to saving the maximum amount of solar energy [ 81 ].

2.8. Nanotechnology and Textiles Industry

The textile industry achieved glory in the 21st century with enormous outgrowth through social media platforms. Large brands have taken over the market worldwide, and millions are earned every year through textile industries. With the passing of time, nanotechnology is being slowly incorporated into the textile fiber industry owing to its unique and valuable properties. Previously, fabrics manufactured via conventional methods often curtailed the temporary effects of durability and quality [ 82 ]. However, the age of nanotechnology has allowed these fabric industries to employ nanotechnology to provide high durability, flexibility, and quality to clothes which is not lost upon laundering and wearing. The high surface-to-volume ratio of nanomaterials keeps high surface energy and thus provides better affinity to their fabrics, leading to long-term durability [ 82 ]. Moreover, a thin layering and coating of nanoparticles on the fabric make them breathable and make them smooth to the touch. This layering is carried out by processes such as printing, washing, padding, rinsing, drying, and curing to attach nanoparticles on the fabric surface. These processes are carried out to impart the properties of water repellence, soil resistance, flame resistance, hydrophobicity, wrinkle resistance, antibacterial and antistatic properties, and increased dyeability to the clothes [ 83 ].

The unique properties of nanomaterials in textile industries have attracted large-scale businesses for the financial benefits attached to their application. For this reason, competitors are increasing in nanotextile industry speedily, which may make the conventional textile industry sidelined in the near future [ 84 ]. Some benefits associated with nanotextile engineering and industry may include: improved cleaning surfaces, soil, wrinkle, stain, and color damage resistance, higher wettability and strike-through characteristics, malodor- and soil-removal abilities, abrasion resistance, a modified version of surface friction, and color enhancement through nanomaterials [ 85 ].

These characteristics have hugely improved the functionality and performance characteristics of textile and fiber materials [ 86 ]. Based upon the numerous advantages, nanotextile technology is increasingly being used in various inter-related fields, including in medical clothes, geotextiles, shock-resistant textiles, and fire-resistant and water-resistant textiles [ 87 ]. These textiles and fibers help overcome severe environmental conditions in special industries where high temperatures, pressure, and other conditions are adjusted for manufacturing purposes. These textiles are now increasingly called smart clothes due to renewed nanotechnological application to traditional methods [ 88 ].

The increasing demand for durable, appealing, and functionally outstanding textile products with a couple of factors of sustainability has allowed science to incorporate nanotechnology in the textile sector. These nano-based materials offer textile properties such as stain-repellent, wrinkle-free textures and fibers’ electrical conductivity alongside guaranteeing comfort and flexibility in clothing [ 82 ]. The characteristics of nanomaterials are also exhibited in the form of connected garments creation that undergo sensations to respond to external stimuli through electrical, colorant, or physiological signals. Thus, a kind of interconnection develops between the fields of photonic, electrical, textile and nanotechnologies [ 89 ]. Their interconnected applications confer the properties of high-scale performance, lasting durability, and connectivity in textile fibers. However, the concerns of nanotoxicity, the chances of the release of nanomaterials during washing, and the overall environmental impact of nanotextiles are important challenges that need to be ascertained and dealt with successfully in the coming years to ensure wide-scale acceptance and the global broad-spectrum application of nanotextiles [ 90 ].

The global market for the textile industry is constantly on the rise; with so many new brands, the competition is rising in regard to pricing, material, product outlook, and market exposure. Under this scenario, nanotechnology has contributed in terms of value addition to textiles by contributing the properties of water repellence, self-cleaning, and protection from radiation and UV light, along with safety against flames and microorganisms [ 82 ]. A whole new market of smart clothes is slowly taking our international markets along with improvements in textile machinery and economic standing. These advances have effectively established the sustainable character of the textile industry and have created grounds to meet the customer’s demand [ 91 ]. Some important examples of smart clothing originating from the nanotextile industry can be seen in products such as bulletproof jackets, fabric coatings, and advanced nanofibers. Fabric coatings and pressure pads can exhibit characteristics of invisibility and entail a silver, nickel, or gold nanoparticle-based material with inherent antimicrobial properties [ 92 ]. Such materials are effectively being utilized and introduced into the medical industry for bandages, dressings, etc. [ 92 ].

Similarly, woven optical fibers are already making progress in the textile and IT industry. With the incorporation of nanomaterials, optical fibers are being utilized for a range of purposes such as light transmission, sensing technologies, deformation, improved formational characteristic detection, and long-range data transmission. These optical fibers with phase-changing material properties can also be utilized for thermostability maintenance in the fiber industry. Thus, these fibers have combined applications in the computer, IT, and textile sectors [ 93 ]. In addition, the nano cellulosic material that is naturally obtained from plants confers properties of stiffness, strength, durability, and large surface area to volume ratios, which is acquired through the large number of surface hydroxyl groups embedded in nanocellulose particles [ 94 ]. Moreover, the characteristics of high resistance, lower weight, cost-effectiveness, and electrical conductivity are some additional benefits which are also linked to these nanocellulosic fibers [ 93 ]. The aforementioned technologies will allow industrialists to manufacture fabrics based on nanomaterials through a variety of chemical, physical, and biological processes. The scope of improvement in the textile properties, cost, and production methods is making the nanotextile industry a strong field of interest for future industrial investments.

2.9. Nanotechnology and Transport and Automobile Industry

The automotive industry is always improving its production. Nanotechnology is one such tool that could impart the automotive industry with a totally new approach to manufacturing. Automobile shaping could be improved greatly without any changes to the raw materials used. The replacement of conventional fabrication procedures with advanced nanomanufacturing is required to achieve the required outcome. Nanotechnology intends to partly renovate the automobile industry by enhancing the technical performance and reducing production costs excessively. However, there is a gap in fully harnessing the potential of nanomaterials in the automotive industry. Industrialists who were previously strict about automotive industrial principles are ready to employ novelties attached to nanotechnology to create successful applications to automobiles in the future [ 95 ]. Nanotechnology could provide assistance in manufacturing methods with an impartment of extended life properties. Cars that have been manufactured with nanotechnology applications have shown lower failure rates and enhanced self-repairing properties. Although the initial investment in the nanoautomated industry is high, the outcomes are enormous.

The concept of sustainable transport could also be applied to the manufacturing of such nano-based technology which is CO 2 free and imparts safe driving and quiet, clean, and wider-screen cars, which, in the future, may be called nanocars. The major interplay of nanotechnology and the automotive industry comes in the manufacturing of car parts, engines, paints, coating materials, suspensions, breaks, lubrication, and exhaust systems [ 32 ]. These properties are largely imparted via carbon nanotubes and carbon black, which renders new functionalities to automobiles. These products were previously in use, but nanoscaling and nanocoating allow for enhanced environmental, thermal, and mechanical stability to be imparted to the new generation of automobiles. In simple terms, automobiles manufactured with principal nanonovelties could result in cars with less wearing risk, better gliding potential, thinner coating lubrication requirements, and long service bodies with weight reductions [ 31 ]. These properties will ultimately reduce costs and will impart more space for improved automobile manufacturing in the future. Similarly, the development of electric cars and cars built on super capacitor technology is increasingly based on nanotechnology. The implications of nanotechnology in the form of rubber fillers, body frames made of light alloys, nanoelectronic components, nanocoatings of the interior and exterior of cars, self-repairing materials against external pressure, nanotextiles for interiors, and nanosensors are some of the nanotechnological-based implications of the automotive industry [ 96 ]. Owing to these properties, nanotechnology ventures are rapidly progressing in the automobile industry. It is expected that, soon, the automobile industry will commercialize nanotechnological perspectives on their branding strategies.

2.10. Nanotechnology, Healthcare, and Medical Industry

The genesis of nanomedicine simply cannot be ignored when we talk about the large fields of biological sciences, biotechnology, and medicine. Nanotechnology is already making its way beyond the imagination in the broader vision of nanobiotechnology. The quality of human life is continuously improved by the successful applications of nanotechnology in medicine, and resultantly, the entire new field of nanomedicine has come to the surface, which has allowed scientists to create upgraded versions of diagnostics, treatment, screening, sequencing, disease prevention, and proactive actions for healthcare [ 97 ]. These practices may also involve drug manufacturing, designing, conjugation, and efficient delivery options with advances in nano-based genomics, tissue engineering, and gene therapy. With this, it could be predicted that soon, nanomedicine will be the foremost research interest for the coming generation of biologists to study the useful impacts and risks that might be associated with them [ 98 ]. As illustrated in Figure 2 , we summarized the applications of nanotechnology in different subfields of the medical industry.

Nanotechnology applications in medical industry. Nanotechnology has a broad range of applications in various diagnostics and treatments using nanorobotics and drug delivery systems.

In various medical procedures, scientists are exploring the potential benefits of nanotechnology. In the field of medical tools, various robotic characters have been applied which have their origins in nano-scale computers, such as diagnostic surfaces, sensor technologies, and sample purification kits [ 99 ]. Similarly, some modifications are being accepted in diagnostics with the development of devices that are capable of working, responding, and modifying within the human body with the sole purpose of early diagnosis and treatment. Regenerative medicine has led to nanomanufacturing applications in addition to cell therapy and tissue engineering [ 100 ]. Similarly, some latest technologies in the form of ‘lab-on-a-chip’, as elaborated upon earlier, are being introduced with large implications in different fields such as nanomedicine, diagnostics, dentistry, and cosmetics industries [ 101 ]. Some updated nanotechnology applications in genomics and proteomics fields have developed molecular insights into antimicrobial diseases. Moreover, medicine, programming, nanoengineering, and biotechnology are being merged to create applications such as surgical nanorobotics, nanobioelectrics, and drug delivery methods [ 102 ]. All of these together help scientists and clinicians to better understand the pathophysiology of diseases and to bring about better treatment solutions in the future.

Specifically, the field of nanocomputers and linked devices help to control activation responses and their rates in mechanical procedures [ 2 ]. Through these mechanical devices, specific actions of medical and dental procedures are executed accurately. Moreover, programmed nanomachines and nanorobots allow medical practitioners to carry out medical procedures precisely at even sub-cellular levels [ 4 ]. In diagnostics fields, the use of such nanodevices is expanding rapidly, which allows predictions to be made about disease etiology and helps to regulate treatment options [ 103 ]. The use of in vitro diagnosis allows increased efficiency in disease apprehension. Meanwhile, in in vivo diagnoses, such devices have been made which carry out the screening of diseased states and respond to any kind of toxicities or carcinogenic or pathological irregularities that the body faces [ 104 ].

Similarly, the field of regenerative medicine is employing nanomaterials in various medical procedures such as cell therapy, tissue engineering, and gene sequencing for the greater outlook of treatment and reparation of cells, tissues, and organs. Nanoassemblies have been recorded in research for applications in powerful tissue regeneration technologies with properties of cell adhesion, migration, and cellular differentiation [ 102 ]. Additionally, nanotechnology is being applied in antimicrobial (antibacterial and antiviral) fields. The microscopic abilities of these pathogens are determined through nano-scale technologies [ 100 ]. Greek medicinal practices have long been using metals to cure pathogenic diseases, but the field of nanotechnology has presented a new method to improve such traditional medical practices; for example, nanosized silver nanomaterials are being used to cure burn wounds owing to the easy penetration of nanomaterials at the cellular level [ 102 , 105 ].

In the field of bioinformatics and computational biology, genomic and proteomic technologies are elucidating molecular insights into disease management [ 106 ]. The scope of targeted and personalized therapies related to pathogenic and pathophysiological diseases have greatly provided spaces for nanotechnological innovative technologies [ 107 , 108 ]. They also incorporate the benefits of cost-effectiveness and time saving [ 109 ]. Similarly, nanosensors and nanomicrobivores are utilized for military purposes such as the detection of airborne chemical agents which could cause serious toxic outcomes otherwise [ 102 ]. Some nanosensors also serve a purpose similar to phagocytes to clear toxic pathogens from the bloodstream without causing septic shock conditions, especially due to the inhalation of prohibited drugs and banned substances [ 100 , 105 , 110 ]. These technologies are also used for dose specifications and to neutralize overdosing incidences [ 110 ] Nano-scale molecules work as anticancer and antiviral nucleoside analogs with or without other adjuvants [ 21 ].

Another application of nanotechnology in the medical industry is in bone regeneration technology. Scientists are working on bone graft technology for bone reformation and muscular re-structuring [ 111 , 112 ]. Principle investigations of biomineralization, collagen mimic coatings, collagen fibers, and artificial muscles and joints are being conducted to revolutionize the field of osteology and bone tissue engineering [ 113 , 114 ]. Similarly, drug delivery technologies are excessively considering nanoscaling options to improve drug delivery stability and pharmacodynamic and pharmacokinetic profiles at a large scale [ 110 ]. The use of nanorobots is an important step that allows drugs to travel across the circulatory system and deliver drug entities to specifically targeted sites [ 99 , 115 ]. Scientists are even working on nanorobots-based wireless intracellular and intra-nucleolar nano-scale surgeries for multiple malignancies, which otherwise remain incurable [ 102 ]. These nanorobotics can work at such a minute level that they can even cut a single neuronic dendrite without causing harm to complex neuronal networks [ 116 ].

Another important application of nanotechnology in the medical field is oncology. Nanotechnology is providing a good opportunity for researchers to develop such nanoagents, fluorescent materials, molecular diagnostics kits, and specific targeted drugs that may help to diagnose and cure carcinogenesis [ 104 ]. Scientists are trying various protocols of adjoining already-available drugs with nanoparticulate conjugation to enhance drug specificity and targeting in organs [ 104 , 107 , 117 ]. Nanomedicine acts as the carrier of hundreds of specific anticancerous molecules that could be projected at tumor sites; moreover, the tumor imaging and immunotherapy approaches linked with nanomedicine are also a potential field of interest when it comes to cancer treatment management [ 112 , 117 ]. A focus is also being drawn toward lessening the impact of chemotherapeutic drugs by increasing their tumor-targeting efficiency and improving their pharmacokinetic and pharmacodynamic properties [ 112 ]. Similarly, heat-induced ablation treatment against cancer cells alongside gene therapy protocols is also being coupled with nanorobotics [ 99 , 118 ]. Anticancerous drugs may utilize the Enhanced Permeation and Retention Effect (EPR effect) by applications of nano assemblies such as liposomes, albumin nanospheres, micelles, and gold nanoparticles, which confirms effective treatment strategies against cancer [ 119 ]. Such advances in nanomedicine will bring about a more calculated, outlined, and technically programmed field of nanomedicine through association and cooperation between physicians, clinicians, researchers, and technologies.

2.10.1. Nanoindustry and Dentistry

Nanodentistry is yet another subfield of nanomedicine that involves broad-scale applications of nanotechnology ranging from diagnosis, prevention, cure, prognosis, and treatment options for dental care [ 120 ]. Some important applications in oral nanotechnology include dentition denaturalization, hypersensitivity cure, orthodontic realignment problems, and modernized enameling options for the maintenance of oral health [ 2 , 121 ]. Similarly, mechanical dentifrobots work to sensitize nerve impulse traffic at the core of a tooth in real-time calculation and hence could regulate tooth tissue penetration and maintenance for normal functioning [ 122 ]. The functioning is coupled with programmed nanocomputers to execute an action from external stimuli via connection with localized internal nerve stimuli. Similarly, there are other broad-range applications of nanotechnology in tooth repair, hypersensitivity treatment, tooth repositioning, and denaturalization technologies [ 4 , 118 , 120 , 121 ]. Some of the applications of nanotechnology in the field of dentistry are elaborated upon in Figure 3 .

Nanotechnology applications in field of dentistry. Nanotechnology can be largely used in dentistry to repair and treat dental issues.

2.10.2. Nanotechnology and Cosmetics Industry

The cosmetics industry, as part of the greater healthcare industry, is continuously evolving. Nanotechnology-based renovations are progressively incorporated into cosmetics industries as well. Products are designed with novel formulations, therapeutic benefits, and aesthetic output [ 123 ]. The nanocosmetics industry employs the usage of lipid nanocarrier systems, polymeric or metallic nanoparticles, nanocapsules, nanosponges, nanoemulsions, nanogels, liposomes, aquasomes, niosomes, dendrimers, and fullerenes, etc., among other such nanoparticles [ 101 ]. These nanomaterials bring about specific characteristics such as drug delivery, enhanced absorption, improved esthetic value, and enhanced shelf life. The benefits of nanotechnology are greatly captured in the improvement of skin, hair, nail, lip, and dental care products, and those associated with hygienic concerns. Changes to the skin barrier have been largely curtailed owing to the function of the nano scale of materials. The nanosize of active ingredients allows them to easily permeate skin barriers and generate the required dermal effect [ 124 ].

More profoundly, nanomaterials’ application is encouraged in the production of sun-protective cosmetics products such as sunblock lotions and creams. The main ingredient used is the rational combination of cinnamates (derived from carnauba wax) and titanium dioxide nanosuspensions which provide sun-protective effects in cosmetics products [ 125 ]. Similarly, nanoparticle suspensions are being applied in nanostructured lipid carriers (NLCs) for dermal and pharmaceutical applications [ 126 ]. They exhibit the properties of controlled drug-carrying and realizing properties, along with direct drug targeting, occlusion, and increased penetration and absorption to the skin surface. Moreover, these carrier nanoemulsions exhibit excellent tolerability to intense environmental and body conditions [ 127 ]. Moreover, these lipid nanocarriers have been researched and declared safe for potential cosmetic and pharmaceutical applications. However, more research is still required to assess the risk/benefit ratio of their excessive application [ 128 ].

2.11. Nanotechnology Industries and Environment

The environment, society, and technology are becoming excessively linked under a common slogan of sustainable development. Nanotechnology plays a key role in the 21st century to modify the technical and experimental outlook of various industries. Environmental applications cannot stand still against revolutionary applications of nanotechnology. Since the environment has much to do with the physical and chemical world around a living being, the nano scale of products greatly changes and affects environmental sustainability [ 129 ]. The subsequent introduction of nanomaterials in chemistry, physics, biotechnology, computer science, and space, food, and chemical industries, in general, directly impacts environmental sciences.

With regard to environmental applications, the remarkable research and applications of nanotechnology are increasing in the processing of raw materials, product manufacturing, contaminate treatment, soil and wastewater treatment, energy storage, and hazardous waste management [ 130 ]. In developed nations, it is now widely suggested that nanotechnology could play an effective role in tackling environmental issues. In fact, the application of nanotechnology could be implemented for water and cell cleaning technologies, drinking safety measures, and the detoxification of contaminants and pollutants from the environment such as heavy metals, organochlorine pesticides, and solvents, etc., which may involve reprocessing although nanofiltration. Moreover, the efficiency and durability of materials can be increased with mechanical stress and weathering phenomena. Similarly, the use of nanocage-based emulsions is being used for optical imaging techniques [ 131 ].

In short, the literature provides immense relevance to how nanotechnology is proving itself through groundbreaking innovative technologies in environmental sciences. The focus, for now, is kept on remediation technologies with prime attention on water treatment, since water scarcity is being faced worldwide and is becoming critical with time. There is a need for the scientific community to actively conduct research on comprehending the properties of nanomaterials for their high surface area, related chemical properties, high mobility, and unique mechanical and magnetic properties which could be used for to achieve a sustainable environment [ 132 ].

2.12. Nanotechnology—Oil and Gas Industry

The oil and gas industry makes up a big part of the fossil industry, which is slowly depleting with the rising consumption. Although nanotechnology has been successfully applied to the fields of construction, medicine, and computer science, its application in the oil and gas industry is still limited, especially in exploration and production technologies [ 133 ]. The major issue in this industry is to improve oil recovery and the further exploitation of alternative energy sources. This is because the cost of oil production and further purification is immense compared to crude oil prices. Nanotechnologists believe that they could overcome the technological barriers to developing such nanomaterials that would help in curtailing these problems.

Governments are putting millions of dollars into the exploration, drilling, production, refining, wastewater treatment, and transport of crude oil and gas. Nanotechnology can provide assistance in the precise measurement of reservoir conditions. Similarly, nanofluids have been proven to exhibit better performance in oil production industries. Nanocatalyses enhance the separation processing of oil, water, and gases, thus bringing an efficient impurity removal process to the oil and gas industry. Nanofabrication and nanomembrane technologies are excessively being utilized for the separation and purification of fossil materials [ 134 ]. Finally, functional and modified nanomaterials can produce smart, cost-effective, and durable equipment for the processing and manufacturing of oil and gas. In short, there is immense ground for the improvement of the fossil fuel industry if nanotechnology could be correctly directed in this industry [ 135 ].

2.13. Nanotechnology and Renewable Energy (Solar) Industry

Renewable energy sources are the solutions to many environmental problems in today’s world. This makes the renewable energy industry a major part of the environmental industry. Subsequently, nanotechnology needs to be considered in the energy affairs of the world. Nanotechnologies are increasingly applied in solar, hydrogen, biomass, geothermal, and tidal wave energy production. Although, scientists are convinced that much more needs to be discovered before enhancing the benefits of coupled nanotechnology and renewable energy [ 136 ].

Nanotechnology has procured its application way down the road of renewable energy sources. Solar collectors have been specifically given much importance since their usage is encouraged throughout the world, and with events of intense solar radiation, the production and dependence of solar energy will be helpful for fulfilling future energy needs. Research data are available regarding the theoretical, numerical, and experimental approaches adopted for upgrading solar collectors with the employment of nanotechnologies [ 137 ].

These applications include the nanoengineering of flat solar plates, direct absorption plates, parabolic troughs, and wavy plates and heat pipes. In most of these instruments and solar collection devices, the use of nanofluids is becoming common and plays a crucial role in increasing the working efficiency of these devices. A gap, however, exists concerning the usage of nanomaterials in the useful manufacturing design of solar panels and their associated possible efficiencies which could be brought to the solar panel industry. Moreover, work needs to be done regarding the cost-effectiveness and efficiency analyses of traditional and nanotechnology-based solar devices so that appropriate measures could be adopted for the future generation of nanosolar collectors [ 138 ].

2.14. Nanotechnology and Wood Industry

The wood industry is one of the main economic drivers in various countries where forest growth is immense and heavy industrial setups rely on manufacturing and selling wood-based products [ 139 ]. However, the rising environmental concerns against deforestation are a major cause for researchers to think about a method for the sustainable usage of wood products. Hence, nanotechnology has set its foot in the wood industry in various applications such as the production of biodegradable materials in the paper and pulp industry, timber and furniture industry, wood preservatives, wood composites, and applications in lignocellulosic-based materials [ 140 ]. Resultantly, new products are introduced into the market with enhanced performance (stronger yet lighter products), increased economic potential, and reduced environmental impact.

One method of nano-based application in the wood industry is the derivation of nanomaterials directly from the forest, which is now called nanocellulose material, known broadly for its sustainable characteristics [ 141 ]. This factor has pushed the wood industry to convert cellulosic material to nanocellulose with increased strength, low weight, and increased electromagnetic response along with a larger surface area [ 142 ]. These characteristics are then further used as reinforcing agents in different subcategories of wood-based industries, including substrate, stabilizer, electronics, batteries, sensor technologies, food, medicine, and cosmetics industries [ 143 ]. Moreover, functional characteristics such as the durability, UV absorption, fire resistance, and decreased water absorption of wood-based biodegradable products are also being improved with the application of nanomaterials such as nanozinc oxide or nanotitanium oxide [ 144 ]. Similarly, wood biodegradable properties are reduced through the application of nanoencapsulated preservatives to improve the impregnation of wood with the increasing penetration of applied chemicals and a reduced leaching effect.

Cellulosic nanomaterials exhibit nanofibrillar structures which can be made multifunctional for application in construction, furniture, food, pharmaceuticals, and other wood-based industries [ 145 ]. Research is emerging in which promising results are predicted in different industries in which nanofibers, nanofillers, nanoemulsions, nanocomposites, and nano-scaled chemical materials are used to increase the potential advantages of manufactured wood products [ 146 ]. The outstanding properties of nanocellulusice materials have largely curtailed the environmental concerns in the wood industry in the form of their potential renewable characteristics, self-assembling properties, and well-defined architecture. However, there are a few challenges related to such industries, such as cost/benefit analyses, a lack of compatibility and acceptability from the public owing to a lack of proper commercialization, and a persistent knowledge gap in some places [ 145 ]. Therefore, more effort is required to increase the applications and acceptability of nano-based wood products in the market worldwide.

2.15. Nanotechnology and Chemical Industries

Nanotechnology can be easily applied to various chemical compositions such as polymeric substances; this application can bring about structural and functional changes in those chemical materials and can address various industrial applications including medicine, physics, electronics, chemical, and material industries, among others [ 76 , 132 , 138 ]. One such industrial application is in electricity production, in which different nanomaterials driven from silver, golden, and organic sources could be utilized to make the overall production process cheaper and effective [ 147 ]. Another effective application is in the coatings and textile industry, which has already been discussed briefly. In these industries, enzymatic catalysis in combination with nanotechnology accelerates reaction times, saving money and bringing about high-quality final products. Similarly, the water cleaning industry can utilize the benefits of nanomaterials in the form of silver and magnetic nanoparticles to create strong forces of attraction that easily separate heavy material from untreated water [ 148 ]. Similarly, there is a wide range of chemicals that can be potentially upgraded, although the nano scale for application in biomedical industries is discussed under the heading of nanotechnology and medicine.

Another major application of nanotechnology in the chemical industry includes the surfactant industry, which is used for cleaning paper, inks, agrochemicals, drugs, pharmaceuticals, and some food products [ 149 ]. The traditional surfactant application was of great environmental and health concern, but with the newer and improved manufacturing and nanoscaling of surfactants, environmentally friendly applications have been made possible. These newer types may include biosurfactants obtained via the process of fermentation and bio-based surfactants produced through organic manufacturing. More research is required to establish the risks and side effects of these nanochemical agents [ 3 ].

3. Closing Remarks

Nanotechnology, within a short period, has taken over all disciplinary fields of science, whether it is physics, biology, or chemistry. Now, it is predicted to enormously impact manufacturing technology owing to the evidential and proven benefits of micro scaling. Every field of industry, such as computing, information technology, engineering, medicine, agriculture, and food, among others, is now originating an entire new field in association with nanotechnology. These industries are widely known as nanocomputer, nanoengineering, nanoinformatics, nanobiotechnology, nanomedicine, nanoagriculture, and nanofood industries. The most brilliant discoveries are being made in nanomedicine, while the most cost-effective and vibrant technologies are being introduced in materials and mechanical sciences.

The very purpose of nanotechnology, in layman’s terms, is to ease out the manufacturing process and improve the quality of end products and processes. In this regard, it is easy and predictable that it is not difficult for nanotechnology to slowly take out most of the manufacturing process for industrial improvement. With every coming year, more high-tech and more effective-looking nanotechnologies are being introduced. This is smoothing out the basis of a whole new era of nanomindustries. However, the constructive need is to expand the research basis of nanoapplications to entail the rigorous possible pros of this technology and simultaneously figure out a method to deal with the cons of the said technology.

The miniaturization of computer devices has continued for many years and is now being processed at the nanometer scale. However, a gap remains to explore further options for the nanoscaling of computers and complex electronic devices, including computer processors. Moreover, there is an immense need to enable the controlled production and usage of such nanotechnologies in the real world, because if not, they could threaten the world of technology. Scientists should keep on working on producing nanoelectronic devices with more power and energy efficiency. This is important in order to extract the maximum benefits from the hands of nanotechnology and computer sciences [ 5 ].

Under the influence of nanotechnology, food bioprocessing is showing improvement, as proven by several scientific types of research and industrial applications in food chain and agricultural fields. Moreover, the aspect of sustainability is being introduced to convert the environment, food chains, processing industries, and production methods to save some resources for future generations. The usage of precision farming technologies based upon nanoengineering, modern nano-scale fertilizers, and pesticides are of great importance in this regard. Moreover, a combined nanotechnological aspect is also being successfully applied to the food industry, affecting every dimension of packing, sensing, storage, manufacturing, and antimicrobial applications. It is pertinent to say that although the applications of nanotechnology in the food, agriculture, winemaking, poultry, and associated packaging industries are immense, the need is to accurately conduct the risk assessment and potential toxicity of nanomaterials to avoid any damage to the commercial food chains and animal husbandry practices [ 63 ].

The exposure of the nano-based building industry is immense for civil and mechanical engineers; now, we need to use these technologies to actually bring about changes in those countries in which the population is immense, construction material is depleting, and environmental sustainability problems are hovering upon the state. By carefully assessing the sustainability potential of these nanomaterials, their environmental, hazardous, and health risks could be controlled, and they could likely be removed from the construction and automobile industry all over the world with sincere scientific and technical rigor [ 150 ]. It is expected that soon, the construction and automobile industry will commercialize the nanotechnological perspectives alongside sustainability features in their branding strategies. These nano-scale materials could allow the lifecycle management of automotive and construction industries with the provision of sustainable, safe, comfortable, cost-effective, and more eco-friendly automobiles [ 32 ]. The need is to explore the unacknowledged and untapped potential of nanotechnology applications in these industry industries.

Similarly, nanotechnology-based applications in consumer products such as textile and esthetics industries are immense and impressive. Professional development involves the application of nanotechnology-based UV-protective coatings in clothes which are of utmost need with climatic changes [ 73 ]. The application of nanotechnology overcomes the limitations of conventional production methods and makes the process more suitable and green-technology-based. These properties have allowed the textile companies to effectively apply nanotechnology for the manufacture of better products [ 90 ]. With greater consumer acceptability and market demand, millions are spent in the cosmetic industry to enable the further usage of nanotechnology. Researchers are hopeful that nanotechnology would be used to further upgrade the cosmetics industry in the near future [ 123 ].

Furthermore, the breakthrough applications of nanomedicine are not hidden from the scientific community. If nanomedicine is accepted worldwide in the coming years, then the hope is that the domain of diagnosis and treatment will become more customized, personalized, and genetically targeted for individual patients. Treatment options will ultimately become excessive in number and more successful in accomplishment. However, these assumptions will stay a dream if the research remains limited to scientific understanding.

The real outcome will be the application of this research into the experimental domain and clinical practices to make them more productive and beneficial for the medical industry. For this cause, a combined effort of technical ability, professional skills, research, experimentation, and the cooperation of clinicians, physicians, researchers, and technology is imperative. However, despite all functional beneficial characteristics, work needs to be done and more exploration is required to learn more about nanotechnology and its potential in different industries, especially nanomedicine, and to take into account and curtail the risks and harms attached to the said domain of science.

Additionally, climatic conditions, as mentioned before, along with fossil fuel depletion, have pushed scientists to realize a low-energy-consuming and more productive technological renovation in the form of nanoengineered materials [ 48 ]. Now, they are employing nanomaterials to save energy and harvest the maximum remaining natural resources. There is immense ground for the improvement of the fossil fuel industry if nanotechnology could be correctly directed in this industry [ 135 ]. The beneficial applications within the solar industry, gas and oil industry, and conversion fields require comparative cost-effectiveness and efficiency analyses of traditional and nano-based technologies so that appropriate measures could be adopted for the future generation of nano-based products in said industries [ 138 ].

As every new technology is used in industries, linked social, ethical, environmental, and human safety issues arise to halt the pace of progress. These issues need to be addressed and analyzed along with improving nanotechnology so that this technology easily incorporates into different industries without creating social, moral, and ethical concerns. Wide-scale collaboration is needed among technologists, engineers, biologists, and industrials for a prospective future associated with the wide-scale application of nanotechnology in diversified fields.

4. Conclusions

Highly cost-effective and vibrant nanotechnologies are being introduced in materials and mechanical sciences. A comprehensive overview of such technologies has been covered in this study. This review will help researchers and professionals from different fields to delve deeper into the applications of nanotechnology in their particular areas of interest. Indeed, the applications of nanotechnology are immense, yet the risks attached to unlimited applications remain unclear and unpronounced. Thus, more work needs to be linked and carefully ascertained so that further solutions can be determined in the realm of nanotoxicology. Moreover, it is recommended that researchers, technicians, and industrialists should cooperate at the field and educational level to explore options and usefully exploit nanotechnology in field experiments. Additionally, more developments should be made and carefully assessed at the nano scale for a future world, so that we are aware of this massive technology. The magnificent applications of nanotechnology in the industrial world makes one think that soon, the offerings of nanotechnology will be incorporated into every possible industry. However, there is a need to take precautionary measures to be aware of and educate ourselves about the environmental and pollution concerns alongside health-related harms to living things that may arise due to the deviant use of nanotechnology. This is important because the aspect of sustainability is being increasingly considered throughout the world. So, by coupling the aspect of sustainability with nanotechnology, a prosperous future of nanotechnology can be guaranteed.

Funding Statement

K.M.’s work is supported by United Arab Emirates University-UPAR-Grant#G3458, SURE plus Grant#3908 and SDG research programme grant#4065.

Author Contributions

Conceptualization, Y.W. methodology, S.M. validation, S.M., K.M. and Y.W. formal analysis, S.M., K.M. and Y.W. investigation, S.M., K.M. and Y.W. resources, K.M. and Y.W. data curation, S.M., K.M. and Y.W. writing—original draft preparation, S.M. writing—review and editing, S.M., K.M. and Y.W. supervision, Y.W. project administration, K.M. and Y.W. funding acquisition, Y.W. and K.M. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Informed consent statement, data availability statement, conflicts of interest.

The authors declare no conflict of interest.

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• Open access
• Published: 20 March 2023

Analytical methods for assessing antimicrobial activity of nanomaterials in complex media: advances, challenges, and perspectives

• Xuzhi Zhang 1 ,
• Xiangyi Hou 2 , 3 ,
• Liangyu Ma 1 ,
• Yaqi Shi 3 ,
• Dahai Zhang 3 &
• Keming Qu 1  

Journal of Nanobiotechnology volume  21 , Article number:  97 ( 2023 ) Cite this article

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Metrics details

Assessing the antimicrobial activity of engineered nanomaterials (ENMs), especially in realistic scenarios, is of great significance for both basic research and applications. Multiple analytical methods are available for analysis via off-line or on-line measurements. Real-world samples are often complex with inorganic and organic components, which complicates the measurements of microbial viability and/or metabolic activity. This article highlights the recent advances achieved in analytical methods including typical applications and specifics regarding their accuracy, cost, efficiency, and user-friendliness. Methodological drawbacks, technique gaps, and future perspectives are also discussed. This review aims to help researchers select suitable methods for gaining insight into antimicrobial activities of targeted ENMs in artificial and natural complex matrices.

Introduction

The twenty-first century has witnessed rapid developments in nanotechnology. Applications of engineered nanomaterials (ENMs) continue to expand in construction, electronics, agriculture, environment, food, consumer product, health care, energy, and medicine [ 1 , 2 , 3 ]. These ENMs have great potential to improve quality of life. Their small size, high surface energy, high surface-to-volume ratio, and high grain boundary atomic rate make them dissimilar from their bulk phase and therefore favorable for use [ 2 , 3 , 4 ]. The same properties also lead to concerns about potential toxicological and adverse effects [ 4 , 5 , 6 , 7 ]. They are reportedly prone to interactions with cell membranes, proteins, DNA, and cellular organelles [ 2 ]. Will the societal and commercial advantages be outweighed by potential disadvantages? To answer this question, accurate insight into the eco-toxicity of ENMs is needed [ 6 , 7 , 8 , 9 ]. In recent decades, extensive research has investigated the toxicity of ENMs towards biota [ 7 , 9 ] to provide reliable data for risk assessments [ 6 , 10 , 11 ].

Bacteria are useful bio-reporters for assessing the toxicity of ENMs [ 12 , 13 ] because they are (1) very important for geobiochemistry and humans, (2) ubiquitous, (3) susceptible to changes of environmental factors, and (4) easy to handle. The simple structures and short life-cycles offer clear advantage over other bio-reporters for performing high throughput screening [ 12 , 13 , 14 ]. Moreover, many kinds of ENMs are designed as novel antibiotics to counteract bacteria [ 2 , 3 , 15 , 16 , 17 , 18 , 19 ].

The toxicity of ENMs towards bacteria has been studied extensively [ 13 , 14 , 15 , 16 ]. In most cases, the effects of ENMs on bacterial viability and/or metabolic activity are analyzed in simple laboratory media [ 2 , 15 , 20 , 21 , 22 , 23 , 24 ]. It is increasingly clear that their toxic efficiency depends on not only the shape, size and physicochemical properties of ENMs themselves and target bacterial cells but also on physical factors and chemical/biological components in the test scenarios [ 2 , 11 , 16 , 25 ] such as temperature, pH, ionic strength, organic matters, and inorganic matter [ 25 , 26 , 27 , 28 , 29 ]. In most applications and concerned eco-systems, ENMs encounter bacterial cells in highly complex media with various inorganic and organic components [ 2 ]. The results of these interactions cannot be predicted with data obtained in simple laboratory media [ 30 ].

Samples from realistic scenarios, e.g., soil, natural water, sediment, sludge, consumer products, food, blood, and biotic tissue, are often complex in physical and chemical features; and thus complicate measurements of microbial viability and/or metabolic activity. Determining the antimicrobial activity of ENMs in realistic samples is far more difficult than in simple laboratory media. As has been well-reviewed by Westmeier et al. [ 2 ], though many classical and emerging methods can be used to determine the antimicrobial activity of ENMs, only a few of these methods can complete tasks where complex samples are involved [ 11 , 16 , 31 ]. Currently, comprehensive information on these determination methods is not available. In this review, we do not attempt to cover the substantial body of relevant literature in this field, but rather to review the recent advances achieved in analytical methods for assessing the antimicrobial activity of ENMs in complex matrices. The accuracy, cost, efficiency and user-friendliness of applied and emerging methods are described along with drawbacks, technique gaps and future perspectives. All figures are reprinted with permission from related publishers/authors.

Applied methods

Methods used to assess the antimicrobial activity of ENMs usually refer to the antibiotic susceptibility testing (AST). In general, phenotypic AST methods provide a direct indication of the susceptibility of a given microbe to an agent at defined concentrations; in some cases, such methods provide a quantitative assessment of the minimal inhibitory concentration (MIC) of the antibiotic. In contrast, genotypic methods are used to describe methods that detect proteomic or genomic signatures that predict antimicrobial resistance [ 32 ]. To date, there are few reports on genotypic methods for assessing the antimicrobial activity of ENMs in complex matrices. Here, we divide these phenotypic methods into two patterns: off-line measurements and on-line measurements. For the former, microbial viability and/or metabolic activity are measured after the model cells are exposed to target ENMs for expected terms. In other words, information on the inhibition, if there is any, results from endpoint measurements of microbial viability and/or metabolic activity. For the latter, microbial viability and/or metabolic activity are measured on-line during the exposure process of ENMs to microbes without sampling operation. Information on the inhibition, if there is any, results from the microbial response in an undisturbed incubation. Note that the complexity of samples from realistic scenarios often makes analytical methods ill-suited for accurately assessing the antimicrobial activity of ENMs [ 31 ]. Moreover, the physicochemical properties of ENMs are significantly different from that of antibiotics. Therefore, each method has differences between the AST of common antibiotics and the antimicrobial activity test of ENMs especially when pretreatments are needed.

In real-world samples, the cell structure and physiological property of microbes vary widely. The physicochemical properties of present ENMs are also variable [ 30 ], and biotic and abiotic matter are complex and variable as well [ 16 ]. As such, researchers must select suitable approaches for these various conditions. To obtain optimal results, various pretreatment and optimization steps are needed. In some cases, a combination of different methods can compensate for the drawbacks and limitations of individual methods [ 2 ]. It is impossible to discuss analytical methods in detail for all types of ENMs and microbes. Here, we present typical off-line methods and on-line methods that are essential for assessing the antimicrobial activity of ENMs in complex matrices. The principles mentioned herein aim to help the reader to understand best practices in assessing the antimicrobial activity of ENMs.

Non-biased approaches are critical when discussing the performance of various analytical methods. This is not an easy task due to the diversity of the reported protocols, of the ENMs to be assessed, of the species of microbes to be evaluated, and of the realistic scenarios of interest. Here, important criteria for comparing different methods include both experimental feasibility and practical values.

Off-line measurement

After short-term or long-term exposure to target ENMs, the viabilities and/or metabolic activities of microbes are measured at the endpoint with or without pretreatments. Media can be sampled for dozens of times during the exposure process for longitudinal information on microbial viability and/or metabolic activity. These time-dependent values are often used to understand how target ENMs affect the kinetics of microbial growth.

Endpoint measurements (i.e., bacterial viability) obtained after microbial exposure to target ENMs for selected periods of time are usually manageable because this correction factor can be applied to exclude the contribution of ENMs to the measured signal. There is also a possibility of combining various analytical methods so that reference methods (i.e., plate counting) are used along an alternative testing approach to correlate and validate the results.

Visualization and optical methods

Most methods for evaluating the viabilities and/or metabolic activities of microbes are based on the principle of optics: visualization, microscopy, imaging, fluorescence, spectrophotometry or their combinations. Such analytical methods are summarized in Table 1 . Here, visualization and optical methods, including plate counting, disc diffusion, microscopy, fluorescence and optical density (OD), are reviewed, mainly based on their read-out features and applications. We also discuss some classical examples in more detail, including various special processes with essential pretreatments before measurements. We refer readers to original publications for unabridged statements.

Plate counting

Plate counting, i.e., culturing and colony counting, is a well-established culture-dependent method for qualitative investigation of microbes. It is often used to measure the microbial viability after an exposure to target ENMs in complex matrices via live cells [ 29 , 33 , 34 , 35 , 36 ]. A classical operation is given by Kusi et al. [ 35 ]: Treated sediment is added to Milli-Q water in centrifuge tubes and vortexed to detach microbes from the sediment particles. The tubes remain undisturbed for 30 min to allow sediment particles to settle and leave detached microbes in the supernatant. The supernatant is then diluted and inoculated into agar broth in Petri dishes. The plates are incubated at a desired temperature for 48 h, and colonies are counted at the endpoint. Figure  1 A shows typical pictures of such a characterization [ 34 ].

A Effect of berberine-cinnamic acid nanoparticle-modified packaging films on E. coli and S. aureus were characterized via a plate-counting method [ 34 ]. B Disc diffusion image of the antimicrobial assessment of CuO nanoparticles against bacterial species [ 37 ]. C Confocal laser scanning microscopy images of bacterial cells in activated sludge after an exposure to TiO 2 nanoparticles: d 1 mg/L Ru-sun and e 1 mg/L An-sun [ 41 ]. D Flow cytometry cytogram of activated sludge cells stained with SYBR Green I + PI [ 41 ]

The plate counting method is sensitive, easy and requires no expensive instruments. However, it requires relatively long culture times to allow the microbes to multiply sufficiently to form visible colonies. The manual readout is vulnerable to human error, less accurate and labor-intensive [ 31 ]. It may produce improper results during the evaluation of highly aggregated microbial cells [ 53 ]. Furthermore, despite the high recovery of bacteria (85–93%) from the original freshwater sediment via separation methods [ 54 ], the accuracy and reproducibility are still questionable. Thus, plate counting has largely been replaced when measuring the MICs of ENMs against microbes in complex matrices.

Disc diffusion

Disc diffusion is low cost, simple, flexible and easy to interpret [ 38 , 53 ]; it is popular for assessing in vitro antimicrobial activity of ENMs in laboratory media [ 15 , 55 ] as well as in complex matrices [ 37 , 38 ]. For example, Turakhia et al . [ 37 ] used this method to assess the antibacterial activity of CuO nanoparticles modified on cotton fabrics. Briefly, cotton fabric samples modified with CuO nanoparticles were planted on an agar plate containing LB agar medium. The plates were inoculated with bacteria and incubated for 24 h. Zones of inhibition were then measured. The diameter revealed the sensitivity of microbes to the incorporated CuO nanoparticles (Fig.  1 B). In general, to accurately assess the antimicrobial activity, aseptic instruments and materials must be used to prevent any false-negative results due to unwanted microbes [ 53 ].

The use of the disc diffusion method for assessing the antimicrobial activity of ENMs is questionable because the low diffusivity of materials practically prevents them from penetrating through the culture media. Kourmouli et al . [ 55 ] found that the disc diffusion method did not show any antibacterial effects of Au nanoparticles due to their negligible diffusivity through the culture media. In contrast, Ag nanoparticles exhibited a strong antimicrobial activity because the antimicrobial behavior was attributed to the ions that they release, thus dissolving upon oxidation and dilution in aqueous solutions. Cavassin et al . [ 15 ] reported that the diffusion method could be used as a screening test rather than as a reference test.

Microscopy is popular because it can visualize structural details. Further, microscopy can characterize the effect of antibiotics by counting cell numbers and morphologies [ 32 , 56 ]. Echavarri-Bravo et al . [ 39 ] assessed the results of ENMs-microbe reactions in a microcosm experiment established with seawater and sediment samples. Ag nanoparticles and model marine bacteria were added to the water column. Total bacterial abundance in the water column was quantified at different time points by direct counts using epifluorescence microscopy and DAPI (4′, 6-diamidino-2-phenylindole) staining. This method requires staining of a relatively large number of microbial cells and is not precise in species identification [ 53 ]. Additionally, it has a low throughput in screening and requires harsh fixation, sometimes involving chemical cross-linking, drying, and high vacuum [ 16 ]. Low throughput and lack of standardization make inter-laboratory comparisons difficult, thus potentially leading to contradictory results [ 2 ].

Fluorescence-based methods

Microbial viability and/or metabolic activity can also be determined via fluorescence intensity. Fluorescence-based methods are more accurate than counting-based methods for determining adherent cells [ 57 ]. Table 1 shows various fluorescence-based methods used to assess the antimicrobial activities of ENMs: imaging (fluorescence confocal laser scanning microscopy), high throughput screening, flow cytometry, and ATP assays.

Imaging: Imaging characterizes the morphological changes in microbial cells. Confocal laser scanning microscopy rejects the light that does not come from the focal plane, thus enabling one to perform optical slicing and construction of three-dimensional (3D) images [ 58 ]. Confocal combines viability staining and detailed image analysis [ 40 , 41 ].

SYTO9 and propidium iodide (PI) are DNA dyes. Green fluorescent SYTO9 is membrane-permeable, whereas red fluorescent PI is not membrane permeable and quenches SYTO9 [ 40 , 41 , 42 , 43 , 44 ]. Li et al . [ 41 ] assessed the results of an ENMs–microbe reaction with imaging patterns by staining samples with SYTO9 and PI. After separating the microbes from the sludge, they performed live/dead staining according to the manufacturer’s instructions of the BacLight live/dead bacterial viability kits. Live bacteria were stained by SYTO 9 and fluoresced green; the dead bacteria were stained by PI and fluoresced red. The original floc structure was observed under a confocal laser scanning microscope, and representative images of bacterial cells in activated sludge after exposure to TiO 2 nanoparticles are shown in Fig.  1 C.

High throughput screening: A decrease in the ratio of fluorescent signals produced by SYTO9 (green) and PI (red) indicates a decrease in the number of live bacterial cells. The antimicrobial activity of ENMs can be accessed by reading the green-to-red fluorescence ratio of tested samples with a high throughput microplate reader [ 42 , 43 , 44 ]. In prior work, ENMs were added to lake water samples containing live bacteria. The mixtures were then incubated in the wells of clear bottom microplates. After the incubation, the SYTO9/PI mixture was added into each well of the microplates and mixed thoroughly. These microplates were then incubated for 15 min at room temperature in the dark followed by fluorescence measurements using a microplate reader. The green-to-red fluorescence ratio was calculated, and a calibration curve was obtained using bacterial mixtures with known percentages of live cells [ 42 ]. Chen et al . [ 44 ] reported no interference with BacTiter-Glo and BacLight assays in the case of testing 0.4 mg/L CuO nanoparticles and 2 mg/L TiO 2 nanoparticles. However, the concentrations of microbes were not high enough for accurate assessments of natural lake or river water samples with this method. Consequently, pretreatment steps, e.g., centrifugation or filtration, were always needed before the incubation [ 43 ].

ATP-based method: ATP derives its inherent energy secondary to anhydride bonds connecting adjacent phosphate functional groups. It transports chemical energy within cells for various metabolic purposes. Live cells contain ATP, and ATP assays can measure live microbes quantitatively [ 59 ].

Some research groups have used simple-to-use ATP-based assays to characterize the effects of ENMs on microbes in environmental water samples even at very low concentrations (e.g., < 20 μg/L [ 60 ]) where cell death was not apparent [ 44 , 45 , 46 , 60 ]. Generally, BacTiter-Glo microbial cell viability assays can quantify ATP levels by measuring the luminescence signal intensity from the reaction of luciferin and ATP. Briefly, ENMs and liquid samples containing bacterial cells were incubated at room temperature. After the incubation, BacTiter-Glo reagent was mixed in each well, and the plate was covered with aluminum foil and incubated for 5 min before measuring luminescence with a microplate reader [ 44 ].

Resazurin-based method: The non-fluorescent phenoxazine dye resazurin can be taken up by live cells. The metabolic activity of microbial cells reduces resazurin to red fluorescent resofurin. The application of resazurin to check the microbial viability is of particular interest because it is non-toxic, easy to handle and requires relatively little preparation time [ 47 , 61 , 62 ]. Ahmed et al. [ 47 ] assessed the acute toxicity effects of graphene oxide on the wastewater bacterial community. Briefly, activated sludge samples were incubated with resazurin and exposed to different concentrations of graphene oxide in a 96-well flat bottom plate. The production of resofurin was quantified with a microtiter plate reader at 530/587 nm to assess the inhibition of metabolic activity by the ENMs.

Flow cytometry: Flow cytometry is useful in cell counting, cell sorting, chromosome preparation and biomarker detection in a stream of fluid [ 63 ]. It can help researchers detect almost all bacteria including non-culturable species, and reliably distinguishes and quantitates live and dead bacteria via a flow cytometer in a mixed population containing various bacterial types. Flow cytometry can provide morphometric and functional properties of the target microbes [ 31 ] by considering the light scattering and excitation/emission spectra of different fluorescent materials such as FRET dyes, fluorophores or fluorescent proteins [ 56 ]. This enables faster processing versus conventional methods—changes in physiological parameters are caused by ENMs and are faster than growth inhibition processes (1–2 h vs 16–24 h) [ 48 ]. This method has been applied to several microbial species and combinations of ENMs using various dye/fixation combinations [ 40 , 41 , 48 , 49 ].

It is difficult to identify individual microbial cells within non-fluid samples, e.g., sludge, by flow cytometry assays due to the variety, density, similarity of cells and non-biological particles. Thus, the preparation of detectable cell suspensions is an essential prerequisite. Li et al . [ 41 ] used dilution and sonication to completely disaggregate flocs and release free cells in the bulk liquid. The free cell suspension was filtered with a 20-µm membrane to eliminate coarse particles that might clog the nozzle of the flow cytometer. The resulting free cell suspension was then diluted with buffer to reach a suitable cell concentration for flow cytometry assays. Multicolor fluorescence combined with a dual-staining was used to distinguish subpopulations of bacteria after TiO 2 nanoparticle exposure. The researchers identified live cells by staining with SYBR Green I/PI. The output resulted in a red versus green fluorescence cytogram showing single live (SGI + PI − ) and necrotic (SGI − PI + ) bacteria and lysed cell debris (SGI − PI − ) (minimal fluorescence) distributions (Fig.  1 D). Of note, this work [ 41 ] did not describe the recovery of bacteria from the sludge nor the accuracy/reproducibility of the technique.

Assessing the antimicrobial activities of ENMs in fluid samples with flow cytometry assays is easier than in non-fluid ones. After addition of Ag nanoparticles into natural seawater samples, Doiron et al. [ 48 ] counted bacteria in samples with an EPICS ALTRATM cell sorting flow cytometer with a 488-nm laser. Each sample was directly stained with SYBR Green I without any pretreatment steps for separation. Cells were incubated for 30 min at room temperature in the dark followed by flow cytometry analysis. Fluorescent beads were systematically added to each sample as an internal standard to normalize cell fluorescence emission. To quantify bacteria, the volume analyzed was calculated by weighing samples before and after each run. Total free bacteria were detected in a plot of green fluorescence recorded at 530 nm ± 30 nm versus side angle light scatter.

Flow cytometry can quantify the antimicrobial activity of ENMs within a few hours, but it is rarely used due to inefficiencies with complex samples, especially meat, sludge, sediment, fabrics and soil. The staining inefficiency of dyes and autofluorescence are also key challenges [ 56 ].

OD method: In theory, when a light beam passes through a bacterial suspension in a clear solution, the scattered or absorbed light detected by a spectrophotometer correlates with bacteria density. Thus, the OD measurement is an alternative to nondestructively quantify target microbes [ 56 , 64 ]. It is one of the most important and viable methods that can be potentially adapted into a high-throughput format for rapidly measuring bacterial cells after exposure to ENMs [ 50 , 51 , 52 , 65 ]. This turbidity pattern can be easily adjusted for special culture conditions [ 66 ]. This phenotypic method strictly follows the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines for AST, which is a major advantage [ 56 ]. A few multichannel automated machines, e.g., BD Phoenix, Vitek and BAXTER MicroScan, are commercially available for high throughput tests [ 32 , 56 , 67 , 68 ]. For example, turbidity-based BD Phoenix can use up to 99 channels [ 69 ].

Recently, Chavan et al . [ 50 ] used the OD method to assess the effects of Ag nanoparticles, ZnO nanoparticles and TiO 2 nanoparticles on bacterial communities in soil. Briefly, soil samples from a microcosm were shaken for 30 min in sterile saline. The solution was then further diluted and transferred to a plate for one week of incubation. The OD 590 of the solution was measured with a microplate spectrophotometer every 24 h. Finally, the OD 590 of the well was corrected by subtracting the control (no substrate) well at the same reading time. To investigate the bactericidal activity of CuO nanoparticles integrated with cotton fabrics, Shaheen et al . [ 52 ] developed a special OD method. Cotton fabrics coated with ENMs were immersed in liquid culture media, in which target bacterial cells were inoculated. The OD 630 of the liquid culture media was then measured at a desired interval during the incubation. The bacterial growth in the nutrient medium was considered to be proportional to the OD values. Thus, the antimicrobial activity of CuO nanoparticles was calculated after an incubation of 24 h.

There are several important issues when using the OD method to assess the antimicrobial activity of ENMs in complex matrices: (1) The OD method is not suitable for low concentrations of bacteria [ 56 ]; (2) It cannot distinguish between live cells and dead cell debris [ 31 ]; (3) It is limited by cells forming chains, clumps (e.g. Streptomyces koyangensis ), filaments, or aggregates; and is difficult to perform in complex media that can lead to light scattering or absorption and thus interference [ 39 , 70 ]; (4) It is almost impossible to separate ENMs from biological samples without disturbing cell viability [ 65 ]; and (5) Scattering and absorbance from ENMs (e.g., arginine-functionalized gold composite nanoparticles [ 62 ]) act as interferences that complicate quantitative analysis [ 65 , 71 ]. Pan et al . [ 31 ] commented that OD measurements were the most unreliable method to quantify the bacteria in the presence of ENMs.

We note that due to the unique physicochemical properties and increased reactivity of ENMs, there is a high potential for these materials to interfere with almost all kinds of spectrophotometric and spectrofluorometric measurements, thus leading to data artefacts and subsequent incongruent estimations of antimicrobial activities [ 72 ].

Molecular test-based methods

Molecular tests for antimicrobial activity research utilize molecular markers that are indicative of the presence of microbes and/or resistance. The vast majority of molecular tests in this area use quantitative and qualitative nucleic acid and protein markers via PCR, sequencing, metagenomics analysis and enzymatic viability analysis. Versus culture-based methods, the major advantage of molecular-based methods is that they reduce turnaround times for the culture step [ 67 , 73 ]. Furthermore, they are particularly popular where non-culturable or slowly growing microbes are involved [ 67 ]. These assessments of antimicrobial activity are indirect because these values are calculated from molecular marker responses rather than from the quantitative and/or qualitative values of microbes.

Nucleic acid analysis

Developments in DNA/RNA analysis technologies, such as PCR, qPCR, RT-PCR, and high-throughput sequencing, have facilitated rapid microbe identification and characterization in genomes and metagenomes. They provide opportunities for rapid determinations of cultivable and uncultivable microbes from complex matrices. Table 2 describes nucleic acid analysis to assess the antimicrobial activity of ENMs in fluids, semi-fluids, and non-fluid matrices.

A small minority of the gene analysis-based methods are used to assess the antimicrobial activities of ENMs by quantifying single microbial species [ 29 ] or special genes [ 74 ]. Herein, we select Qin et al . [ 29 ] as a representative example. Briefly, E. coli in aquatic environment samples were homogenized, and the total RNA was extracted using an RNA extraction kit and quantified using a UV–VIS spectrophotometer. The RNA quality was monitored with agarose gel electrophoresis. The cDNA was synthesized using a cDNA synthesis kit. A qPCR assay was performed with 16S rDNA primers as a housekeeping gene and served as an internal control for tested gene expression analysis. Gene expression was calculated using the 2 −ΔΔCt method. Significant differences in the tested gene expression were assessed by one-way analysis of variance (ANOVA) followed by Tukey's HSD test using SPSS software.

Most gene analysis-based methods analyze whole genes extracted from complex matrices [ 43 , 48 , 51 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. Researchers obtain detailed information about bacterial community structure, relative abundance and/or diversity via an amplification and analysis of 16S rRNA genes. They then infer the antimicrobial activities of target ENMs against the entire bacterial community. In general, in the case of fluid complex matrices, the experimental operation consists of separation of microbial cells (by centrifuge or filter), a cells lysis step, extraction and purification of genomic DNA, amplification and final data analysis via a computer and special software(s). Here, we selected Doiron et al . [ 48 ] to show the procedure with a final DGGE DNA analysis. Briefly, seawater samples were filtered with a polycarbonate membrane. Total DNA was extracted from the filter after a cell lysis step. PCR amplification of the 16S rDNA gene was performed using universal primers. Amplicons were then purified with special columns and stored until DGGE analysis. DGGE was performed using a DGGE-4001-Rev-B system. Gels were then stained with a half-diluted solution of SYBR Green I for 1 h and photographed under UV light. Finally, DGGE profiles were analyzed using Phoretix 1D Pro software to show bacterial richness. From the information on bacterial richness, the authors inferred the effect of Ag nanoparticles on the bacterial community structure. We also highlight Londono et al . [ 79 ] to illustrate sequencing. Here, microbes were filtered from river water and subjected to DNA extraction. The DNA concentration and quality were checked with a Nanodrop spectrophotometer. PCR amplification of the 16S rDNA gene was performed using the HotStarTaq Plus Master Mix Kit. Next-generation DNA sequencing was conducted by Molecular Research systems. An in-house proprietary analysis pipeline was used to process the sequence data. The remaining sequences were then denoised, and chimeras were removed using UCHIME implemented in Mothur software. The operational taxonomic units were taxonomically classified using BLASTn against a database derived from NCBI and RDPII and compiled into each taxonomic level into both “count” and “percentage” files. Sequence counts by taxa were further analyzed using R—a free software environment for statistical computing and graphics. Microbial community differences between groups were tested for significance using the two-factor Adonis function of the vegan package. Heat maps were created to illustrate microbial distribution in tested samples using hierarchical clustering of relative abundance. Species richness was determined by a genera or species taxa count in each sample. The Shannon index for species diversity in a given community for each tested condition was calculated using the diversity function in the Vegan package, and species evenness was calculated as the Shannon index divided by the natural logarithm of species richness.

A completed separation of live microbial cells is very difficult in non-fluid complex matrices (e.g., sludge and soil). Usually, chemical and biological reagents are directly added into the matrices to lyse microbial cells [ 84 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. The total DNA/RNA is then extracted from the complex matrices. A few commercial kits can facilitate this task. The remaining experimental operations (DNA purification, amplification, gene analysis) are similar to that for fluid matrices. We select Nuzzo et al . [ 77 ] as an example of the determination procedure with a final DGGE DNA analysis. Briefly, slurry samples were centrifuged and the water phase was discarded; metagenomic DNA was extracted from the wet sediment with a Power Soil DNA extraction kit. 16S rRNA genes of the bacterial community were amplified using PCR with special primers. DGGE of bacterial amplicons were performed with a D-Code apparatus with a denaturing gradient from 40 to 60% denaturant. Gels were stained with SYBR Green I and their image was captured in UV transilluminator with a digital camera. Community richness and organization indexes were calculated from DGGE image analysis.

Miao et al . [ 87 ] reported a typical procedure with a sequencing analysis for assessing the effect of ENMs on bacterial community in soil. Briefly, wet sediments were collected and frozen with ethanol and dry ice. Genomic DNA was extracted using a tissue DNA kit. The concentration of extracted DNA was measured with a NanoDrop and Pico Green assays. Subsequently, real-time qPCR was used to determine the copy numbers of the 16S rRNA gene of all bacteria in the sediment with the fluorescent dye SYBR green approach. The bacterial community was investigated by Illumina high-throughput sequencing. The raw data were saved as paired-end fastq and raw fastq files were demultiplexed using QIIME. After removing the barcodes and primers, the data were subsampled to 13,876 sequences per sample to avoid biases related to unequal numbers of sequences. The normalized samples were then individually classified and analyzed by the RDP Classifier.

RNA can also be used as a biomarker. For instance, Chen et al . [ 75 ] extracted total RNA from the centrifuged sludge pellets. They performed a reverse transcription PCR with specific primers to obtain the cDNA before amplification of bacterial 16S rRNA genes.

Here, we emphasize a few important issues in gene analysis research.

Not all genetic materials extracted from natural complex samples are sourced from live cells. There may be some environmental DNA (eDNA), i.e., the genetic material present in environmental samples, such as sediment, water, and air, including whole cells as well as extracellular DNA released from dead cells [ 96 ]. eDNA is reported to persist for days, weeks or years in environmental samples [ 97 ]. PCR assays cannot discriminate between live and dead cells [ 98 ]. Future work should accurately quantify gene copy number from live microbes perhaps via coexisting extracellular DNA in the complex matrices [ 99 ]. Propidium monoazide can intercalate into double stranded DNA and form covalent linkages, thus resulting in chemically modified DNA that cannot be amplified by PCR [ 100 , 101 ]. However, the intercalation requires exposure of blue light. Thus, the addition of propidium monoazide cannot be used in most complex matrices (e.g., sludge and sediment) because light cannot penetrate into the sample.

DNA and RNA can rapidly adsorb onto all known ENMs when entering complex physiological or ecological environments [ 102 ]. Thus, it is questionable to quantify the antimicrobial activities of ENMs via PCR analysis due to the interference of ENMs with PCR amplification [ 100 ]. Thus, inhibitory concentration values based on the concentration–response relationship cannot be derived via gene analysis [ 81 ].

The cost is rather high due to the need for expensive reagents and machinery with specific maintenance conditions. Few units are available for point-of-care use. Thus, a transfer of samples is required.

Note that most of these gene analysis-based methods involve complex workflows (e.g., cell separation, cell lysis, DNA/RNA separation, genetic materials purification, amplification and sequencing analysis). Technological hurdles remain despite automation. Upstream sample processing is difficult to be automated [ 67 ]. These manual and semi-manual steps have a prerequisite of skilled personnel. Furthermore, these cumbersome steps cause slow turnaround times. For instance, DNA extraction and library preparation can still take up to 5 h prior to sequencing analysis [ 103 ].

One of the key prerequisites are prior sequence data of the specific target gene to estimate the changes of microbial diversity, community structure, richness and relative abundance based on the data of gene analysis [ 53 ]. This means that the reliability of the measurement depends on the perfection of professional databases rather than the method itself.

Protein analysis

Apart from nucleic acid markers, protein (enzyme)-based molecular signatures can also be used to assess the antimicrobial activities of ENMs in complex matrices via suitable readout approaches. This field has benefited from protein analysis, e.g., lactate dehydrogenase (LDH) kits are widely available to measure LDH released by damaged cells [ 72 ]. Table 3 summarizes protein analysis-based methods to assess the antimicrobial activities of ENMs in complex matrices, e.g., natural water, soil and sediment.

Enzymes have important biochemical and microbiological roles in natural matrices. Enzyme activity assays can measure the antimicrobial activities of ENMs. A common procedure was reported by Xu et al . [ 89 ]. Briefly, sediment samples were mixed with the needed chemical reagents for urease activity detection. Ultrapure water was added after incubation. The supernatant was filtered, and the ammonium concentration of the filtered extracts was determined by measuring the absorbance with a UV–vis spectrophotometer. The value of the enzyme activity was calculated with a working curve. Finally, the antimicrobial activity of target ENMs in complex matrices was evaluated based on the change of enzyme activities. Recently, reagent kits for facilitating these tasks have become commercially available [ 88 , 94 ].

Protein analysis is less complicated than gene analysis, as it requires fewer reagents and instruments, thus leading to a medium cost. However, the stability of the results still depends on the operator skill level. In general, protein analysis lacks sensitivity because of the absence of an amplification step [ 53 ].

Common issues of molecular test-based methods

One of the primary issues impacting molecular tests may be the interference resulting from ENMs themselves [ 100 ], thus leading to data artefacts and subsequent incongruent estimations of antimicrobial activity. These inconsistent and/or inaccurate data make it difficult for regulators to establish guidelines and procedures, ultimately hindering our ability to predict how ENMs will affect organisms in complex matrices [ 72 ].

These methods are relatively expensive and require cumbersome steps such as cell lysis, genetic materials/protein separation, purification and transfer. Even skilled professionals cannot completely avoid all objective and subjective errors.

There are few studies on the recovery of the extraction of genetic materials and separation of protein from complex matrices. In theory, it is impossible to guarantee recovery and reproducibility. Therefore, these methods are rare in quantifying the inhibitory effect of ENMs against target microbes and microbial communities.

It is impossible to perform on-line monitoring. Thus, molecular tests act as a powerful supplementary tool rather than replacing phenotypic susceptibility testing.

Mass test-based methods

The analysis of the microbial mass change resulting from exposure is an alternative method for assessing antimicrobial activities of ENMs. The microbial mass change can be inferred from the mass change of total DNA [ 104 , 107 ], protein [ 49 , 108 ] and other biomarkers (e.g., ergosterol [ 109 ]), which are separated from the tested complex matrices.

Grün et al . [ 104 ] assessed the effect of Ag nanoparticles on microbes in soil. They extracted and purified genomic DNA with a commercial soil kit to measure the change of microbial biomass. For the measurement of microbial biomass, 10 μL of DNA was transferred into the well of a 96-well microplate and shaken for 5 s before absorbance was measured at 260 nm. Das et al . [ 108 ] measured bacterial production from protein synthesis using 3 H-leucine incorporation. Briefly, subsamples from the Ag nanoparticle addition experiment were incubated for 1 h with 3 H-leucine. Incubations were stopped by the addition of formalin. Bacterial cells were harvested by filtration onto 0.22-mm polycarbonate membrane filters, and proteins were precipitated with repeated washing with tricholoracetic acid. The radioactivity of each filter was assessed by liquid scintillation counting and counts converted to micrograms C/L/d. Note that specific bacterial production estimates could not be determined. To the best of our knowledge, there are still no reports that directly measured microbial mass separated from tested matrices before and after exposure.

Versus molecular test-based methods, these methods are simpler and more cost-effective. However, the results also depend on operators’ skill level. In addition, we cannot find any critical analytical properties (e.g., recovery, sensitivity, accuracy and reproducibility) of these methods. In theory, it is hard to use them for quantitative analysis because it is impossible to guarantee recovery and reproducibility.

Respiration-based methods

Methods based on microbial respiration, including the heterotrophic respiration [ 39 , 81 , 87 , 88 , 110 ] and the metabolic quotient [ 111 ], have been reported for assessing antimicrobial activities of ENMs in soil and sediment. For instance, heterotrophic respiration of biofilm communities was measured in sediment cores using a DO sensor. The sensor was placed ~ 1 cm from the water/sediment interface, and oxygen concentrations were recorded after sealing the sediment core. The amount of consumed oxygen was calculated over time and averaged over all repeated measurements. The resulting values obtained were used to infer the effect of CuO nanoparticles against biofilm communities [ 88 ]. A basal respiration assay was performed in another report [ 111 ]. Pre-incubated test soil was added to sterilized glass vials prepared for four incubation periods; these were then capped with a rubber septum. At the time of sampling, the vials were sampled by removing 1 mL of headspace with an airtight syringe. The headspace sample was injected into a CO 2 /H 2 O analyzer and the time and resulting observed peaks were recorded to calculate the rate of CO 2 released per gram of soil. The metabolic quotient (qCO 2 ) was calculated as a ratio of respiration to biomass (qCO 2  = respiration/biomass) to assess the effect of Ag nanoparticles on microbial activity.

Respirometry assays can be applied to measure the O 2 uptake of the entire microbial community inhabiting the matrices and can provide insight into the overall physiological status of the community including non-culturable aerobic bacterial groups. These assays can also provide information about the immediate bacterial response within 0.5 h of temporal resolution. Respirometry is simpler and more cost-effective than molecular and mass-based methods; however, it has low precision and reproducibility (Fig.  2 ) [ 39 ].

The O 2 uptake changes of microbial communities during the course of the microcosm exposing to ENMs; results are expressed as the mean value of the O 2 uptake ± S.D [ 39 ]

On-line measurement

A common feature of all methods reviewed above is that they rely on off-line measurement. These methods cannot monitor microbial growth kinetics with high temporal resolution in the presence of ENMs due to the long measurement turnaround time. In realistic scenarios, microbes live in communities such as biofilms, mats, and flocs with an intricate structure created by a diverse consortium of bacterial, Archaean, fungal, and algal species attached to a substratum and embedded within a matrix of extracellular polymeric substances [ 112 ]. Measuring microbial viability and/or metabolic activity often requires sample pretreatment. These pretreatment steps (e.g., separating for gene analysis) might miss markers with a subsequent influence on the experimental results [ 113 ]. Therefore, common off-line endpoint measurements are insufficient for reliable assessments of the antimicrobial activities of ENMs in most complex matrices. On-line and real-time analysis of microbial susceptibility to ENMs will provide more information for an optimized method than static acquisition of single data points [ 114 ].

Monitoring the morphology changes of ENM-microbe interactions or microbial growth on-line is very difficult in complex matrices due to the difficulty of signal read-out. For instance, the accuracy of automated optical-based methods inevitably suffers from interferences from co-existing substances and bacterial clumps [ 62 ]. To date, there are no commercially available instruments and automated phenotypic methods to monitor microbial growth in complex matrices, e.g., soil, sludge, blood and food [ 2 ]. However, pioneering studies like luminescence- [ 115 , 116 ] and electronic sensor-based methods [ 71 , 117 ] have recently been reported (Table 4 ).

Luminescence-based methods

Mallevre et al . [ 115 , 116 ] used the switch-off Pseudomonas putida ( P. putida ) BS566::luxCDABE bioreporter as a model bacteria to assess the antimicrobial activity of ENMs in wastewater. In brief, bacteria were pre-cultured overnight under shaking conditions in wastewater and then freshly diluted to reach a final concentration. Stock suspensions of Ag nanoparticles were serially diluted to give final tested concentrations. All wastewater samples were supplemented with D-glucose prior to use to ensure a consistent minimal amount of carbon source. Assays were conducted in black walled 96-well microtiter plates. Monitoring of the emitted luminescence evolution of P. putida was performed using a SpectraMax M5 reader in a kinetic mode for 2 h. Results were expressed in relative luminescence (% RLU) and plotted against time for selected conditions. Ag nanoparticle toxicity was expressed as IC 50 at 1 h.

The operation of the luminescence-based method is easy because of the absence of sampling. No expensive instruments are needed other than the spectra reader. The growth curves provide detailed information on the bacteria inhibition of the ENMs at each growth stage, thus enabling users to directly read out IC 50 values. However, the accuracy and precision are poor (see the error bar in Fig.  3 ) [ 116 ]. This method is thus limited to transparent liquid matrices.

Real time monitoring of Ag nanoparticle toxicity in wastewater [ 116 ]. Relative luminescence output evolutions over time by P. putida BS566::luxCDABE when challenged up to 200 mg/L ENMs in a crude and b final wastewaters. Data are mean ± standard error of the mean (n = 4)

Electronic sensor-based methods

Our group constructed an automated phenotypic method to directly determine the antimicrobial activity of ENMs by developing multi-channel contactless conductometric sensors (CCS) [ 71 , 117 ]. The working window of the contactless conductometric sensor covers the conductivity range of simple laboratory solutions and common realistic aqueous samples. It allows simultaneous cultivation and on-line monitoring of the kinetic process of bacterial growth in the presence of ENMs and provides high temporal resolution growth curves. As such, the automated phenotypic method enables users to directly obtain accurate MIC (the principle is shown in Fig.  4 ). Briefly, to determine the bacteriostatic activity of ENMs, modified river or sea water samples containing E. coli or S. aureus cells were loaded in disposable testing tubes. The ENMs were added into individual tubes to make a series of concentrations. All tubes were then simultaneously inserted into the CCS. The capacitively coupled contactless conductivity of the aqueous media in each tube was collected at a rate of 0.5 min. A sigmoidal growth curve was then generated by plotting the conductivity values as a function of incubation time. The bacteria growth may be completely inhibited at high concentrations (≥ MIC) of ENMs, thus leading to a straight line [ 114 ]. This sensing method highlights the advantages of universality, simplicity and affordability and is a new field of analytical chemistry for determining the antimicrobial activity of ENMs. However, it should be validated with real samples before use to determine accurate MICs for risk assessments of ENMs in realistic scenarios.

Schematic diagrams of the automated CCS method for determining the antimicrobial activity of ENMs [ 71 ]. In both simple and modified river and sea water, the growth kinetics of model bacteria ( E. coli and S. aureus ) were determined to generate growth curves that enable users to directly obtain MICs ( a ). Insert: Test tubes loaded with aqueous samples are inserted in the CCS. The capacitively-coupled contactless conductivities of the liquid samples are monitored on-line in a non-invasive way. When the concentration of target ENMs is below the MIC, a sigmoidal growth curve is generated by plotting conductivity values as a function of incubation times ( b ). No conductivity changes in the medium leads to a straight line when the concentration of target ENMs is equal or higher than the MIC ( c )

Emerging alternatives

In theory, the assessment of ENMs’ antimicrobial activity is similar to the AST. However, not all AST methods are suitable for this task. For instance, Kourmouli et al. [ 55 ] found that disc diffusion susceptibility testing was not suitable for assessing the antimicrobial activity of Au nanoparticles. Likewise, many analytical methods have been used to characterize the results of ENMs-microbe interactions [ 2 ]. Of these, only a few are suitable for determining the results of interactions in complex matrices, especially non-fluid samples mainly due to nonhomogeneous conditions [ 113 ]. The need for sample pretreatment contributes substantially to the variation of readout, thus increasing measurement errors.

In this context, we provide some promising recommendations for measuring microbial viability and/or metabolic activity in the presence of ENMs in complex matrices. These emerging techniques have the likelihood to yield fast, reliable and reproducible data on ENMs-cell responses in vitro. The criterion for our recommendations is the theoretical feasibility and practical value rather than the number of papers published per technique.

On-line monitoring-based methods

Hyperspectral imaging.

Hyperspectral imaging (Fig.  5 A [ 118 ]) analyzes a wide spectrum of light instead of only assigning primary colors (red, green, blue) to each pixel. The light striking each pixel is broken down into many different spectral bands to provide more information on the sample. In dark-field microscopy, targets are uniquely identified by light scattering patterns of cells, thus providing high signal-to-noise ratios to acquire cellular images from the background [ 119 ]. On a microscopic level, cellular images are generated with a hyperspectral microscope and serve as the bacteria’s “fingerprint”; theoretically, any pathogen can be detected with a spectral fingerprint using hyperspectral images once a reference library from pure bacterial isolates has been created. This technique can directly detect live bacteria in complex matrices such as chicken rinsate [ 119 ] and pork meat [ 120 ]. Data on total viable counts of bacteria in pork as a function of storage time were generated using a hyperspectral imaging method (Fig.  5 B). Hyperspectral imaging has also been used to analyze the kinetics of Ag ion leaching from nanoparticles [ 121 ].

Hyperspectral imaging system [ 118 ] A and the change of total viable count of bacteria in pork meat with storage time monitoring with the hyperspectral imaging system ( B ) [ 120 ]

Raman spectroscopy

Raman spectroscopy, especially surface-enhanced Raman spectroscopy (SERS), is an attractive approach for biological sensing due to its high sensitivity, real-time response, and capacity for molecular fingerprinting [ 122 , 123 , 124 , 125 , 126 ]. It provides a simple and even quantitative manner to monitor the microbial activity and the associated responses of activity to antibiotics [ 126 ].

Weidemaier et al . [ 124 ] reported an approach for the real-time detection and identification of pathogens in complex culture matrix. In brief, SERS-labeled immunoassay nanoparticles were present in the cultural enrichment vessel, and the signal was monitored in real-time through the wall of the vessel during culture. This continuous monitoring of a specific microbe loaded throughout the enrichment process enabled rapid and hands-free detection without interfering with microbial growth, thus significantly reducing the risk of contaminating the surrounding environment. Wang et al . [ 125 ] reported using SERS for detection of both volatile and nonvolatile metabolites. This approach was used to quantify bacterial growth. The time-dependent SERS signal of the volatile metabolite dimethyl disulfide in the headspace above bacteria growing on an agar plate was detected and quantified on-line.

Raman spectroscopy is feasible for assessing the antimicrobial activity of ENMs even in complex matrices; it does not interfere with microbial growth. However, the robustness of the SERS signal is dependent on the ability to concentrate the plasmonic particles in the area of the laser. For certain matrices with large particulates, care must be taken in the design of the instrument and the magnetic pelleting system to ensure that these particulates do not interfere with reproducible concentration of the plasmonic particles.

Contactless resonator sensor

Similar to contactless conductometric sensors [ 71 , 117 , 127 ], contactless resonator sensors are popular because they non-invasively monitor bacterial growth [ 128 , 129 , 130 ]. Generally, the resonance frequency of an immersed magnetoelastic sensor is measured through magnetic field telemetry; thus, these changes are mainly in response to microbial adhesion. In turn, the decrease allows one to calculate the microbial concentration. The lack of any physical connection between the measurement sensor and the culture medium facilitates aseptic operation and avoids electrode deterioration, thus making the platform ideally suited for on-line monitoring. These methods have been successfully used for rapid and real-time monitoring of bacterial growth against antibiotics in solid growth medium [ 129 ].

Electrochemical sensing

Electrochemical methods offer relatively simple instrumentation, easy miniaturization, cost-effectiveness and easy automation of measurements. They are thus interesting tools for monitoring microbial growth [ 64 , 131 ]. Impedance/capacitance [ 132 , 133 , 134 , 135 , 136 , 137 ] and potentiometry (especial pH-metry) [ 138 , 139 , 140 ] are usually applied because the growth of microbes changes the electrical properties and the strength of the acids. Indirect conductivity can be used to measure CO 2 production as an indicator of microbial growth [ 141 , 142 ].

Impedance/capacitance has been used to monitor bacterial growth on-line in both ideal liquid culture media [ 132 , 133 ] and complex matrices [ 134 , 135 , 136 , 137 ]. These methods can also perform ASTs in nonhomogeneous media [ 135 , 136 ]. For instance, Blanco-Cabra et al . [ 136 ] presented a microfluidic platform with an integrated impedance sensor. This device allowed an irreversible and homogeneous attachment of bacterial cells of clinical origin even directly from clinical specimens. The resulting biofilms were monitored by electrical impedance spectroscopy, thus providing a suitable protocol to study polymicrobial communities as well as to measure the effect of antimicrobials on biofilms without introducing disturbances, thus better mimicking real-life clinical situations (Fig.  6 ).pH-metry is independent of the type of microbes as well as the nature and chemical properties of the substrate used to grow the cells. It has been used to monitor microbial fermentation [ 138 ] and can analyze microbial viability in complex solutions as demonstrated in spiked milk and human whole blood [ 139 ].

Bio-film-chip 3D view ( a ), 3D view of one chamber with the electrodes and one set of 3 chambers ( b ), experimental setup ( c ), changes in the mechanical flow rate and the manual flow rate ( d ), expected relative impedance ( e ), and biofilm formation over time ( f ) [ 136 ]

Actively growing bacteria releases CO 2 metabolites that can change the conductivity of interlinked KOH agar solution. Thus, conductimetric technology can be used to indirectly monitor microbial growth. The Callanan group introduced an indirect conductivity method to study the bacterial growth in complex food matrices [ 141 , 142 ]. The linearity of conductivity responses in selected food products was investigated with good correlation ( R 2  ≥ 0.84) between inoculum levels and times to detection.

Despite these significant advantages, contact electrochemical methods suffer from electrode deterioration and nonspecific binding (the working electrodes must be in galvanic contact with the medium) [ 64 ]. These issues should be considered when researchers use contact electrochemical methods for determining the antimicrobial activity of ENMs. Such invasive measurements may result in erratic results that decrease the accuracy [ 64 , 143 ]. Prior work [ 144 ] offers key tips to solve electrode fouling.

Mass spectrometry

Different species of microbes usually live together in real samples or even in culture medium. Mass spectrometry is a promising method for monitoring the characteristics of different species growth because the microbe’s metabolism leads to the production of highly diverse multiple volatile organic compounds [ 99 , 145 ]. Sovová et al . [ 99 ] monitored population dynamics in concurrent bacterial growth using mass spectrometry quantification of volatile metabolites. The concentrations of volatile metabolites were measured in the headspace of the individual species, and their mixtures were continuously monitored for 24-h periods. The results demonstrated that this method could be utilized to monitor bacterial proliferation in real time without interfering with the living organisms. Mass spectrometry was successfully used for AST in a urinary tract infection [ 146 ] and to study the non-lethal effects of Ag nanoparticles on a gut bacterium [ 147 ] by monitoring bacterial growth. It is reasonable to believe that this method will be useful for determining the antimicrobial activity of ENMs including via portable mass spectrometry [ 148 ].

Electronic nose and electronic tongue

The electronic nose and electronic tongue are combinations of gas and chemical sensors and are non-invasive and portable tools to assess volatile compounds. Gas sensor arrays are ‘electronic noses,’ and chemical sensor arrays are ‘electronic tongues’ [ 144 , 149 ]. Typically, they offer fast response and require little or no sampling operations, making them ideal tools for use as on-line monitoring. The cost of these arrays is relatively lower than chromatography, liquid chromatography and mass spectrometry [ 150 ]. Electronic noses and electronic tongues have been broadly applied in determining microbiological properties, even the process of growth in complex matrices [ 150 , 151 , 152 ]. Thus, they are promising for determining the antimicrobial activity of ENMs provided that their sensitivity and accuracy are improved [ 152 ].

Isothermal microcalorimetry

The microbial growth involves metabolic processes, which generate heat. The heat flow rate is proportional to the reaction rate, and the total heat produced per unit time is proportional to the extent of the reaction taking place in time. This makes isothermal microcalorimetry a useful, non-specific tool for assessing the process of microbial growth in real time with the integration of proper mathematical models [ 64 , 153 , 154 , 155 , 156 ]. For instance, Bonkat et al . [ 153 ] reported an isothermal microcalorimetry method for on-line monitoring of microbial growth that offered continuous data with high temporal resolution. It could detect the metabolic activity of bacteria in complex samples [ 154 ] and perform AST of bioactive glass in powder formulations [ 156 ].

Advanced gene analysis-based methods

Despite the difficulty of real time and accurate measurements due to sampling requirements and other complicated upstream operations, gene analysis has a significant advantage in terms of high-throughput screening [ 136 ]. Gene analysis-based methods will likely remain one of the primary techniques for studying the antimicrobial activity of ENMs in complex matrices over the next decade, especially due to miniaturization of setups and introduction of advanced amplification techniques.

Detection of resistance genes

In general, the mainstream of AST using gene analysis method is attributed to the rapid, direct, sensitive and specific detection of resistance genes [ 32 ]. Unlike common AST, the mainstream of assessing the antimicrobial activity of ENMs relies on the quantification of biomass via amplification and determination of 16S rRNA gene [ 30 ]. The resistance of microbes to ENMs is increasingly studied [ 83 , 86 , 157 , 158 ]. Metch et al . [ 83 ] reported that the E. coli 013, P. aeruginosa CCM 3955, and E. coli CCM 3954 could develop resistance to Ag nanoparticles after repeated exposures. This resistance evolved only a phenotypic change rather than a genetic change. Ewunkem et al . [ 158 ] reported the nature of the genomic changes responsible for the resistance of bacteria to Fe nanoparticles. Prior knowledge of specific resistance genes is present, and thus it will be a promising approach to assess the antimicrobial activity of ENMs by determining special resistance genes.

Rapid and point-of-care gene analysis

Recently, a few isothermal DNA/RNA amplification methods have been developed including loop-mediated isothermal amplification (LAMP), recombinase polymerase amplification (RPA), helicase-dependent amplification (HDA), cross-priming amplification (CPA), nucleic acid sequence-based amplification (NASBA), single primer isothermal amplification (SPIA), rolling circle amplification (RCA) and strand exchange amplification (SEA) [ 67 , 159 ]. Contrary to PCR and sequencing techniques, isothermal techniques are rapid and can be completed on-site for detection in low-resource settings without much processing of samples [ 159 , 160 ]. For assessing the antimicrobial activity of ENMs in complex matrices, they will go beyond PCR-based methods becomes of the attractive efficiency, affordability and user-friendliness.

eDNA technique

eDNA is the DNA directly extracted from environmental samples, including soil, sediment, water or air, without enrichment, which is now being used to detect individual species and communities in ecosystems [ 96 ]. eDNA technologies provides a full spectrum for assessing adverse effects by environmental stressors including that from pollutants at different levels of biological organization. They are a key advanced tool for evaluating the effects of pollutants on wildlife with time/labor savings and non-invasive sampling [ 161 , 162 ].

Integrated comprehensive droplet digital detection

Kang et al . [ 163 ] developed a technology called integrated comprehensive droplet digital detection to rapidly (1–3 h) and selectively detect bacteria directly from a large volume of unprocessed blood in a one-step, culture-free reaction. Their technology integrated real-time, bacterium-detecting fluorescence chemistries, droplet microfluidics and a high throughput particle counter system (Fig.  7 ). Using E. coli as a target, the method could selectively detect both stock isolates of E. coli and clinical isolates in spiked whole blood at single-cell sensitivity. This provides absolute quantification of target bacteria within a broad range of low concentrations with LODs in the single-digit regime [ 67 ]. This method may be used to rapidly measure the results of ENM-microbe interactions.

Schematic of integrated comprehensive droplet digital detection [ 163 ]. a Blood samples and DNAzyme sensors are mixed and then encapsulated in droplets. DNAzyme sensors produce an instantaneous signal in the droplets that contain the bacterium. b Droplets are collected and analyzed using a high-throughput 3D particle counter that permits accurate detection of single-fluorescent droplets in a milliliter pool of non-fluorescent droplets within minutes

Combined methods

There is no single gold standard for characterizing the interaction of ENMs with microbiota. A combination of different analytical methods is highly recommended as a strategy to compensate for the drawbacks and limitations of individual methods [ 2 ]. In some previous studies, more than two methods were frequently used to characterize the effects of ENMs on microbes in complex matrices [ 22 , 36 , 51 , 81 , 87 , 88 , 104 , 111 , 164 , 165 ]. For instance, Samarajeewa et al . [ 81 , 111 , 165 ] combined plate counting, respiration, protein analysis, PCR-DGGE and DNA-sequencing methods to study the effects of ENMs on microbial community in soil. Miao et al . [ 87 , 88 , 164 ] combined confocal laser scanning microscopy, OD, high throughput screening and DNA-sequencing methods to study the effects of ENMs on microbes in complex matrices (e.g., sediment). The multi-aspect characterizations as a consequence of the combination of analytical methods will improve reliability and comprehensiveness.

The full scale and scope of the antimicrobial activity of ENMs in complex matrices are of great significance for both fundamental research and applications. Several methods have been developed to address this task via on-line and off-line measurements. Other promising methods are emerging, thus enabling better characterization in liquid, semi-liquid and non-liquid matrices (Fig.  8 ).

Applied and emerging analytical methods for the assessment of antimicrobial activity of ENMs in complex liquids, semi-liquids, and non-liquid matrices. Applied methods are marked with bright colors. Emerging methods are indicated by pale colors

Ideally, researchers need a method or a few techniques to present reliable and comprehensive results including accurate MIC values. Considering cost, user-friendliness, time consumption, sensitivity, accuracy and stability, we provide some general recommendations on the use of these present methods with the most feasibility to yield appropriate data on ENM-microbe response (Fig.  9 ). Our goal was to provide the community with current information on the most appropriate strategies depending on the particular needs and resources for their experimental setup. Of course, researchers should systematically investigate the performance of their application before the establishment of standard/reference methods with new techniques.

Recommended strategies for assessing antimicrobial activity of ENMs in complex liquids, semi-liquids and non-liquid matrices

To assess the antimicrobial activity of ENMs, common analytical methods were studied in comparison [ 15 , 31 , 100 , 119 ]. These counterpart methods presented remarkably different results for the same sample. To date, no reports have compared results among different laboratories, likely because most studies mainly focused on scientific advancements rather than practical applications. The lack of standardized guidance on the analytical methods exacerbates the uncertainty in antimicrobial activity data interpretation [ 11 , 113 ]. Therefore, international standardization is urgently needed in the fields of ecological environment, food, pharmaceutics and materials science.

Availability of data and materials

Not applicable.

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Acknowledgements

This work was supported by the Key Project of the Natural Science Foundation of Shandong Province (ZR2020KB021), the Key R&D Program of Shandong province (2020CXGC010703) and the National Key R&D Program of China (2019YFD0900505).

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Laboratory for Marine Fisheries Science and Food Production Processes, Pilot National Laboratory for Marine Science and Technology, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, 266071, China

Xuzhi Zhang, Liangyu Ma & Keming Qu

School of Marine Ecology and Environment, Shanghai Ocean University, Shanghai, 201306, China

Xiangyi Hou

Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, Ocean University of China, Qingdao, 266100, China

Xiangyi Hou, Yaqi Shi & Dahai Zhang

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Zhang, X., Hou, X., Ma, L. et al. Analytical methods for assessing antimicrobial activity of nanomaterials in complex media: advances, challenges, and perspectives. J Nanobiotechnol 21 , 97 (2023). https://doi.org/10.1186/s12951-023-01851-0

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Received : 22 February 2022

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DOI : https://doi.org/10.1186/s12951-023-01851-0

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