Toxicity of metal and metal oxide nanoparticles

Environmental Chemistry Letters https://doi.org/10.1007/s10311-020-01033-6 REVIEW Toxicity of metal and metal oxide nanoparticles: a review Ayse Busra Sengul1 · Eylem Asmatulu2 Received: 22 August 2019 / Accepted: 7 June 2020 © Springer Nature Switzerland AG 2020 Abstract Nanotechnology has recently found applications in many fields such as consumer products, medicine and environment. Nanoparticles display unique properties and vary widely according to their dimensions, morphology, composition, agglomeration and uniformity states. Nanomaterials include carbon-based nanoparticles, metal-based nanoparticles, organic-based nanoparticles and composite-based nanoparticles. The increasing production and use of nanoparticles result in higher exposure to humans and the environment, thus raising issues of toxicity. Here we review the properties, applications and toxicity of metal and non-metal-based nanoparticles. Nanoparticles are likely to be accumulated in sensitive organs such as heart, liver, spleen, kidney and brain after inhalation, ingestion and skin contact. In vitro and in vivo studies indicate that exposure to nanoparticles could induce the production of reactive oxygen species (ROS), which is a predominant mechanism leading to toxicity. Excessive production of ROS causes oxidative stress, inflammation and subsequent damage to proteins, cell membranes and DNA. ROS production induced by nanoparticles is controlled by size, shape, surface, composition, solubility, aggregation and particle uptake. The toxicity of a metallic nanomaterial may differ depending on the oxidation state, ligands, solubility and morphology, and on environmental and health conditions. Keywords Nanotechnology · Nanoparticles · Metal nanoparticles · Toxicity mechanism · Reactive oxygen species Introduction Nanotechnology has become one of the most rapidly growing areas of science and technology in the USA as well as other parts of the world. It has led to the increased production and applications of nanomaterials in a wide range of fields such as automotive, biomedical, cosmetics, defense, energy and electronics. The global market for nanotechnology products and applications was valued at $39.2 billion in 2016 and is expected to reach $90.5 billion in 2021 (McWilliams 2016). The nanomaterial is defined as a material with any external dimension in the nanoscale or having an internal structure or surface structure in the nanoscale, approximately 1–100 nm size range (ISO 2015). They may be in the form of nanoparticles, nanofibers, nanotubes, nanocomposites * Eylem Asmatulu [email protected] 1 Department of Civil and Construction Engineering, Kennesaw State University, Kennesaw, GA 30144, USA 2 Department of Mechanical Engineering, Wichita State University, 1845 Fairmount Street, Wichita, KS 67260, USA and nanostructured materials. Figure 1 shows the classification of nanostructure materials according to dimensions, morphology, composition, agglomeration and uniformity states. Nanoparticle agglomeration, size and surface reactivity, along with shape and size, need to be considered when choosing health and environmental regulations for new materials (Asmatulu et al. 2013; Asmatulu 2013). Nanoparticles have been used in many products due to their unique physicochemical properties, which include a large surfaceto-volume ratio, extremely small size and size-dependent optical properties (Sajid et al. 2015). For example, cobalt nanoparticles have gained great interest in biomedicalrelated fields such as drug delivery and magnetic resonance imaging (Ansari et al. 2017). Silica nanoparticles are used in chemical and electronic industries, building materials, foods, and the biomedical and biotechnological fields (Kaphle et al. 2018; Zhou et al. 2019). Titanium dioxide and zinc oxide nanoparticles are frequently used as suncare products to minimize the unwanted skin whitening effect and to provide high UV protection efficacy and pleasant skin aesthetics (Stark et al. 2015). Although the uses of nanoparticles have contributed significant advantages in many areas, nanoparticles raise 13 Vol.:(0123456789) Environmental Chemistry Letters Fig. 1 Classification of nanostructured materials. (1) Dimensionality of nanoparticles; one-dimensional (1D), two-dimensional (2D) and three-dimensional (3D) nanoparticles. (2) Morphology; flatness, sphericity and aspect ratio. (3) Composition; composed of a single- constituent or composite materials. (4) Uniformity and agglomeration: nanomaterials can be dispersed in aerosols, suspensions/colloids or an agglomerate state. Adapted from Buzea et al. (2007) serious concern about exposure and adverse effects on human and the environment. In the recent years, a number of in vitro and in vivo studies have been performed to understand the toxicological impacts and possible hazards of different nanoparticle exposures to human and the environment. There is still a major gap in knowledge about the toxicity effects of nanoparticle exposures. In this review, an overview of the properties and potential applications of metal and non-metal-based nanoparticles is provided and the most recent research studies related to toxic effects of exposure to metal and non-metal-based nanoparticles are highlighted. This article is an abridged version of the chapter by Sengul, A.B., and Asmatulu, E. [Nanomaterials Causing Cellular Toxicity and Genotoxicity, In V. Kumar, P. Guleria, S. Ranjan, N. Dasgupta, and E. Lichtfouse, Nanotoxicology and Nanoecotoxicology] that will be published in the book series Environmental Chemistry for a Sustainable Word (http:// www.springer.com/series/11480). properties but also viewed as the fundamental building blocks of various applications. Carbon-based particles mostly consist of carbon nanotubes, fullerenes and their derivatives, carbon black, nanodiamonds, graphite nanoparticles, graphene nanoparticles and graphene oxide (Patel et al. 2019). These particles have a wide of applications ranging from biomedicine through nanoelectronics to mechanical engineering because of their versatile shapes and various properties like electronic and thermal conductivity (Ema et al. 2016; Sardoiwala et al. 2018). Among all of them, metal-based nanoparticles are the most widely used nanoparticles and are extensively used in different applications such as solar cells, paints, coatings, cosmetics, UV blockers in sunscreen and environmental remediation (EPA 2017). Physiochemical properties, high stability, high reactivity, photothermal and plasmonic properties make metallic nanoparticles an attractive candidate as a therapeutic agent (Sardoiwala et al. 2018). Another group of nanoparticles is organic-based. These well-defined nano-sized polymers are built from branched units capable of being tailored to perform specific chemical functions (Roy and Bhattacharya 2015). Organic-based nanoparticles such as micelles, liposomes, dendrimers and polymers are extensively used in various biosensors/diagnostics, drug delivery, polymer materials, chemical sensors, modified electrodes, DNAtransfecting agents and therapeutic agents for prion diseases (Farré and Barceló 2012; Sandeep 2013). Composite-based 1. Applications of nanoparticles Nanotechnology has attracted great attention in recent years due to its innovative applications in many fields, ranging from consumer products to medicine to improving the environment. Nanoparticles play an important role in nanotechnology, not only because of their unique physicochemical 13 Environmental Chemistry Letters nanoparticles can combine with carbon–carbon nanoparticles, carbon-inorganic nanoparticles and inorganic–inorganic nanoparticles (Jeevanandam et al. 2018). They have novel electrical, catalytic, magnetic, mechanical, thermal and imaging features. Composite-based nanoparticles are used in drug delivery and cancer detection, as well as in auto parts and packaging materials to enhance mechanical and flame-retardant properties. The specific properties and applications of different nanoparticles are summarized in Table 1. The advantageous and disadvantageous of metallic and non-metallic nanoparticles are provided in Table 2. 2. Toxicity mechanisms of nanoparticles The estimated increase in the production and use of nanoparticles will result in their enhanced exposure to humans and the environment. Humans are generally exposed to nanoparticles via inhalation (respiratory tract), ingestion (gastrointestinal tract), skin contact and injection (blood circulation) (Fu et al. 2014; Wu and Tang 2018). Toxicity mechanism of nanoparticles is given in Fig. 2. When nanoparticles enter into the human body, they may cross various cellular barriers and reach the most sensitive organs such as lung, liver and kidney, thus resulting in mitochondrial damage, deoxyribonucleic acid (DNA) mutations and eventually cell apoptosis/ death (Ahamed et al. 2010; Bahadar et al. 2016; Shin et al. 2015; Tan et al. 2018). The production of reactive oxygen species (ROS), which could cause oxidative stress, inflammation and consequent damage to proteins, cell membranes and DNA, is a predominant mechanism leading to toxicity (Fard et al. 2015; Fu et al. 2014; He et al. 2015; Liu et al. 2013; Manke et al. 2013). The level of ROS production induced by nanoparticles is dependent on several factors such as size, shape, surface, composition, solubility, aggregation/agglomeration, particle uptake, the presence of mutagens and transition metals affiliated with the particles (Fu et al. 2014; Gatoo et al. 2014; He et al. 2015; Jeevanandam et al. 2018; Manke et al. 2013; Shvedova et al. 2012). Gliga et al. (2014) revealed size-dependent cytotoxicity of silver nanoparticles since only the 10-nm silver nanoparticles were cytotoxic for the human lung cells starting at doses of 20 μg/mL. However, no coating-dependent cytotoxicity was found between the 10-nm citrate and 10-nm polyvinylpyrrolidone-coated silver nanoparticles. Rizk et al. (2017) found that the liver function enzymes, oxidative stress markers and liver histological pattern were greatly influenced with dose and time of titanium oxide nanoparticles (21 nm), while the genetic disturbance started at the high dose (500 mg/kg body weight) of exposure and for long duration (45 days). Steckiewicz et al. (2019) also demonstrated that the cytotoxicity of gold nanoparticles was shape-dependent. Gold nanostars with the highest anticancer potential were found to be the most cytotoxic, whereas gold nanospheres with small anticancer potential were found to be less toxic. The following part will explain metallic and non-metallic nanoparticles and their toxicity effects. 3. Nanoparticles and Their Toxicity Nanoparticle characteristics (e.g., size and shape), composition, concentration and related toxicity effects are given in Table 3. Human can exposure to nanomaterials with three ways; inhalation into the pulmonary system, absorption through the dermal system and ingestion through the gastrointestinal system. Because of the size and shape, nanoparticles may diffuse quicker in air than their larger counterparts and can get further down the respiratory tract. Inhalation can create great concerns owing to the primary impacts of particulate nanomaterials. The primary consideration is being given to examining impacts on the respiratory and the cardio-vascular framework. Considering dermal entry, healthy skin has a superior obstruction when compared to the respiratory tract system. The hindrance capacity could be constrained by skin injuries, solid mechanical strain or little nanoparticles (< 5–10 nm). Entry by ingestion is of lower concern among the all. Many potential health effects are shown in Fig. 3. Metallic nanoparticles Gold Gold nanoparticles have been widely used in biomedical fields due to their various advantageous and properties such as tunable sizes, facile synthesis, easy modification and strong optical properties (Jia et al. 2017). The outcome regarding gold nanoparticle toxicity is as yet conflicting. Some researcher reported that these particles are biocompatible and have unimportant toxicity (Mukherjee et al. 2016; Negahdary et al. 2015; Nelson et al. 2013; Sung et al. 2011), while others emphasized that they cause ROS leading to oxidative stress and are also highly toxic because of their physicochemical properties (Li et al. 2010; Lopez-Chaves et al. 2018; Thakor et al. 2011; Zhang et al. 2010). Nelson et al. (2013) demonstrated that the citrate-stabilized gold nanoparticles (10, 30 or 60 nm) do not induce discrete, dose-dependent oxidative damage to DNA in either a human liver carcinoma cells or calf thymus-DNA at concentrations less than 0.2 or 2 μg/mL, respectively, nor do they cause cell death or produce free radicals. Senut et al. (2016) found that human embryonic stem cells exposed to 1.5 nm mercaptosuccinic acid-capped gold nanoparticles exhibited loss of cohesiveness, rounding up and detachment resulting in ongoing cell death at concentrations as high as 0.1 μg/mL, whereas other gold nanoparticles (4 and 14 nm) exhibited almost no 13 13 Table 1 Properties and applications of different nanoparticles Type of nanoparticle Examples Carbon-based Specific properties Carbon nano- High thermal and electrical conductivity tubes (CNTs) High tensile strength and elasticity Aspect ratio C60 Antioxidant capacity Radical scavenging Carbon black Reinforcing effects Thermal and electrical conductivity Resistance to UV radiation Antioxidation effect Nanodiamonds Ease of functionalization High biocompatibility Graphene Electrical and thermal conductivity High surface area High strength Good elasticity Ease of functionalization Chemical inertness Gas impermeability Applications References Composites to consumer electronics, energy stor- Ema et al. (2016 and Ma-Hock et al. (2013) age, health care Targeted drug delivery, energy applications, elec- Aschberger et al. (2010) and Ming et al. (2018) tronics, polymer modifications, environment, cosmetic products Sahu et al. (2014) Reinforcement agent in rubber products, black pigment in printing inks and lithography, electrodes for batteries in electrical conductors, finishing process of leather goods production Drug and gene delivery Mengesha and Youan (2013) Gurunathan and Kim (2016 and Ma-Hock et al. Sensors, batteries, fuel cells, supercapacitors, (2013) transistors, components of high-strength machinery, display screens, biomedical applications Environmental Chemistry Letters Type of nanoparticle Examples Specific properties Metal-based NIR-responsive drug delivery, NIR-responsive controlled release, delivery of chemical drugs and genes, theranostic application, promising agents in bioimaging, biosensing and as immunotherapy carriers Antibacterial, antifungal, antiviral and antifilarial Consumer products including electronics, cosmetics, household appliances, textiles and food activity production as well as in biomedical applicaOxidative activity tions such as antimicrobial agents, drug delivery, molecular imaging, biomedical sensing and even cancer photodynamic therapy High magnetism Pigments, catalysts, sensors, magnetic contrast Electrical and catalytic properties agents and in energy storage devices Fuel cells, polymers, paints, coatings, textiles, High hardness biomaterials, batteries, adsorbent, grinding, Mechanical strength catalysis, polishing abrasives Wear resistance Chemical inertness with good biocompatibility Paints, plastics, cosmetics, personal care products Brightness and as food additives and drug delivery agents, High refractive index coatings, papers, inks, medicines, pharmaceutiResistance to discoloration cals, food products, toothpaste Stronger catalytic activity Catalysis, paints, wave filters, UV detectors, Higher chemical activity transparent conductive films, varistors, gas Oxidation resistance sensors, solar cells, sunscreens and cosmetic Corrosion resistance, photocatalysis products Stronger absorption Shielding ability to the ultraviolet rays Superparamagnetic Drug delivery, magnetic resonance imaging, thermal ablation therapy, in vivo cell tracking, magnetic separation of cells or molecules and remediation of different environmental contaminants such as heavy metals, chlorinated organic solvents Au Ag Co Al2O3 TiO2 ZnO IO Tunable sizes Facile synthesis Easy modification Optical properties Applications References Jia et al. (2017) Akter et al. (2018), Cameron et al. (2018), Chen et al. (2015), Foldbjerg et al. (2011) and Guo et al. (2018) Cappellini et al. (2018) and Wan et al. (2017) Future Markets (2013), Kim et al. (2010) and Poborilova et al. (2013) Ranjan and Ramalingam (2016), Shi et al. (2013), Ursini et al. (2014), Weir et al. (2012) and Yin et al. (2012) Guan et al. (2012) and Huang et al. (2010) Feng et al. (2018), Guerra et al. (2018) and Naqvi et al. (2010) Environmental Chemistry Letters Table 1 (continued) 13 13 Table 1 (continued) Type of nanoparticle Examples Specific properties Applications References Organic-based Series of branches Multivalency Globular structure Well-defined molecular weight with controlled surface Small size Biodegradability Water solubility Non-toxicity Long shelf life Stability Fluorescence brightness High photostability Good biocompatibility Large surface area-to-volume ratios Tunable pore size and connectivity Biodegradability Ease of surface modification Biosensors/diagnostics, drug delivery, gene transfection, catalysis Azmi and Shad (2017) and Sandeep (2013) Delivery of drugs, proteins and DNA or genes to specific targeted tissues or organs Yadav et al. (2019) Dendrimers Polymers Composites-based Quantum dots Silica Havrdova et al. (2016) and Matea et al. (2017) Solar cells, photovoltaic devices, light-emitting diode fabrication, photodetectors, computing, biomedical imaging and so on Duan et al. (2013) and Kim et al. (2015) Biomedical and biotechnological fields, such as medical diagnostics, drug delivery, gene therapy, biomolecules detection, photodynamic therapy and bioimaging C60: Fullerene; NP: nanoparticle; Ag: silver; Al2O3: aluminum oxide; Au: gold; Co: cobalt; IO: iron oxide; TiO2: titanium dioxide; ZnO: zinc oxide Environmental Chemistry Letters Environmental Chemistry Letters Table 2 The advantages and disadvantages of metallic and non-metallic nanoparticles Nanoparticle Advantages Metallic Al2O3 Au CuO Ag ZnO IO TiO2 Disadvantages Particles instability: nanomaterials can experience Enrich Rayleigh scattering a transformation since they are in high energy Surface-enhanced Raman scattering local minima and thermodynamically unstable. Great plasma absorption. These cause deterioration of quality, weak corroBiological system imaging sion resistance, and keeping the structure is hard Reveal chemical information on metallic nanoscale Impurity: during the synthesis of nanoparticles, substrate nitrides, oxides, the generation can aggravate Uniformity in shape, size and branch length from the impure nature. Since nanoparticles are highly reactive, there can be high chances of impurity too Biologically harmful: nanomaterials have been toxic, carcinogenic and cause irritation Explosion: exothermic combustion can follow up with an explosion since the fine metal particles behave as strong explosives Difficulty in synthesis: synthesizing of nanoparticles is extremely difficult, so they should be encapsulated Non-metallic C Multiple functions, chemical alteration, biocompatible and water-soluble, effective loading Conductivity and high surface area Carbon nanotube (CNT) Mesoporous High surface area, decent electrostatic immosilica (MS) bilization, immediate adjustment for covalent immobilization Effective carrier system for hydrophilic drug, Polymeric biocompatible, functional alteration, targeting the micelles potential (PMs) References Kumar et al. (2018) Toxicity Kahraman et al. (2017) Difficult functionalization, fragile and aggregation Lamberti et al. (2014) pH sensitivity Kahraman et al. (2017) Occasional cytotoxicity, need of surface alterations Kahraman et al. (2017) Ag: silver; Al2O3: aluminum oxide; Au: gold; C: carbon; CNT: carbon nanotube; CuO: copper oxide; IO: iron oxide; TiO2: titanium oxide; ZnO: zinc oxide Fig. 2 Toxicity mechanism of nanoparticles mediated by reactive oxygen species (ROS) generation. The model describes extracellular sources of ROS as exposure routes for the engineered nanoparticles. Intracellular ROS can be generated from the mitochondria, which later causes lipid peroxidation, DNA damage and protein denaturation toxic effects on the human embryonic stem cells at concentrations as high as 10 μg/mL. Hanna et al. (2018) observed that the majority of gold nanoparticles with a range of sizes (30, 60 and 100 nm) and surface coatings (polyvinylpyrrolidinone, polyethylene glycol, citrate, dendrimers and branched polyethylenimine) tested had little to no impact on nematode 13 13 Table 3 Nanoparticles characteristics and related toxicity mechanisms Physicochemical characterizations Toxicity assays Cells Results Au Shape: rods, stars, spheres Particle size (nm): ≈ 39 nm length, 18 nm width (rods), ≈ 215 nm (stars) ≈ 6.3 nm (spheres) Concentration (μg/mL.): 0.3–5 MTT NR hFOB 1.19 143B MG-63 Ag Allium cepa Shape: Spherical Particle size (nm): ≈ 5, 25, 50, 75 Concentration (mg/L): 100 Hydrodynamic diameter (nm): 42.6 ± 19.2 (5 nm Au), 77.1 ± 26.2 (25 nm Au), 80.5 ± 30.4 (50 nm Au), 124.4 ± 48.1 (75 nm Au) Allium cepa root Co Compositions: Co3O4 nanograins, Co(OH)2 nanoflakes and Co3(PO4)2 microflakes Particle size: 35–40 nm (nanograins), 100 nm (nanoflakes) and 1 μm (microflakes) Concentration (μg/mL): 100 HaCaT Au nanoparticles stars were the most Steckiewicz et al. (2019) cytotoxic, whereas Au nanoparticles spheres were the less cytotoxic ones IC50 values were the lowest for 143B cell line in comparison with hFOB 1.19 and MG-63 cell lines for Au nanoparticles in all investigated shapes Au nanoparticles-induced apoptosis in human osteosarcoma cells, both in 143B and MG-63 Au nanoparticles penetrated through the cell membrane and caused ultrastructural changes Ag nanoparticles-induced alterations Scherer et al. (2019) on the root elongation, germination, mitotic, nuclear abnormality and micronucleus indices MPs permeated the plant cell wall, ending in an increase of the cytotoxic and genotoxic with decreasing the Ag nanoparticles diameter Anwar et al. (2019) Co3(PO4)2 microflakes and Co(OH)2 nanoflakes showed potent amoebicidal activity at 100 and 10 μg/ml against Acanthamoeba castellanii as compared to Co3O4 Encystation and excystation assays showed consistent inhibition at 100 μg/ml Co nanoparticles inhibited amoebaemediated host cell cytotoxicity as determined by LDH release without causing significant damage to human cells when treated alone Amoebicidal Encystation Excystation LDH References Environmental Chemistry Letters Nanoparticles Nanoparticles Physicochemical characterizations Toxicity assays Cells Results Al2O3 Particle size (nm): 20–80 Surface area (m2/g): 40 Hydrodynamic diameter (nm): 303–512 (in Millipore water) Zeta potential (mV): 12.41 (in Millipore water) Concentration (μg/mL): 10, 25, 50 and 100 MTT SOD CAT GSH GST LPO CHSE-214 TiO2 WST-1 Shape: bipyramids, rods, platelets LDH Particle size (nm): 50 ± 9 (bipyramids), 108 ± 47 (rods), 75 ± 25 Comet assay (platelets), 20 ± 5 (P25), 150 ± 50 (food grade) Hydrodynamic diameter (nm): 66 ± 20 (bipyramids), 36 ± 12 (rods), 233 ± 70 (platelets), 107 ± 31 (P25), 184 ± 61 (food grade) Concentration (μg/mL): 5, 10, 20, 50 and 80 20, 50, 80, 120, and 160 μg/mL exposure with light A dose-dependent decline in cell Srikanth et al. (2015) viability was observed in CHSE-214 cells exposed to Al2O3 nanoparticles Oxidative stress induced by Al2O3 nanoparticles in CHSE-214 cells has resulted in the significant reduction of SOD, CAT and GSH in a dose-dependent manner. However, a significant increase in GST and LPO was observed in CHSE-214 cells exposed to Al2O3 nanoparticles in a dose-dependent manner Significant morphological changes in CHSE-214 cells were observed when exposed to Al2O3 nanoparticles at 6, 12 and 24 h Gea et al. (2019) After light exposure, the largest cytotoxicity was observed for rods starting from the dose of 10 μg/ ml; P25, bipyramids and platelets showed a similar cytotoxic effect (doses of 50 μg/ml); no effect was induced by food grade at the tested concentrations No significant LDH release was detected Food grade and platelets induced direct genotoxicity, while P25 (50 μg/ml), food grade (50 μg/ml) and platelets (80 μg/ml) caused oxidative DNA damage No genotoxic or oxidative damage was induced by bipyramids and rods Biological effects were overall lower in darkness than after light exposure. Only food grade, P25 and platelets were internalized by cells, and the uptake resulted correlated with genotoxicity BEAS-2B References Environmental Chemistry Letters Table 3 (continued) 13 13 Table 3 (continued) Nanoparticles Physicochemical characterizations Toxicity assays Cells Results References ZnO Shape: Spherical Size (nm): 30–50 Concentration (μg/mL): 1,5, 10, 15 and 20 Hydrodynamic diameter (nm) in media: 284.76 ± 8.03 Zeta potential (mV): − 12.46 ± 0.28 Flow cytometry MTT DCFH-DA HPRT gene forward mutation Comet assay Micronucleus V-79 ZnO nanoparticles induced oxidative Jain et al. (2019) stress and HGPRT gene mutation All the genotoxicity endpoints such as chromosomal break, DNA damage and mutagenicity were observed at 6 h of ZnO nanoparticle exposure ZnO nanoparticles manifested the cell cycle arrest, ultrastructural modifications and further cell death A significant increase in the apoptotic cells was detected Environmental Chemistry Letters Nanoparticles Physicochemical characterizations Toxicity assays Cells Results References IO Shape: spherical Compositions: PEI and PEG Particle size (nm): 10 and 30 (PEG), 10 (PEI) Concentration (μg/mL): 3.125, 6.250, 12.500, 25.000, 50.00 and 100.000 Hydrodynamic diameter (nm): 17.2 ± 5.0 (PEI 10), 16.5 ± 4.7 (PEG 10), 35.8 ± 10.3 (PEG 30) Zeta potential (mV): + 29.28 (PEI 10), − 0.52 (PEG 10) and − 0.52 (PEG 30) MTS Hoechst 33342 and PI staining LDH Annexin V-FITC/PI staining DCF-DA PEI-coated IO nanoparticles exhibited Feng et al. (2018) In vitro: RAW264.7 significantly higher uptake (after 4-h SKOV-3 incubation) than PEGylated ones In vivo: Nu/Nu strain, BALB/c mice in both RAW264.7 and SKOV-3 cells and caused dose-dependent severe cytotoxicity through multiple mechanisms such as ROS production (at the concentrations ranging from 5 to 20 μg/mL) and apoptosis (after 24-h incubation) 10 nm PEGylated IO nanoparticles showed higher cellular uptake than 30 nm ones and were slightly cytotoxic only at high concentrations PEGylated IO nanoparticles but not PEI-coated IO nanoparticles were able to induce autophagy All the IO nanoparticles tended to distribute in the liver and spleen, and the biodegradation and clearance of PEGylated IO nanoparticles in these tissues were relatively slow (> 2 weeks) 10 nm PEI-coated IO nanoparticles showed the lowest uptake in tumor tissue, whereas 10 nm PEGylated IO nanoparticles achieved the highest tumor uptake, followed by 30 nm PEGylated IO nanoparticles No obvious toxicity was found for PEGylated IO nanoparticles in BALB/c mice, whereas PEI-coated IO nanoparticles exhibited dosedependent lethal toxicity Environmental Chemistry Letters Table 3 (continued) 13 13 Table 3 (continued) Nanoparticles Physicochemical characterizations Pt Toxicity assays Results MTS Particle size (nm): ≈ 70 DCFH-DA Composition: citrate Agglomerate size (nm) in media: 112.4 ± 7.0 Zeta potential (mV) in media: − 12.2 ± 0.9 Concentration (μg/mL): 5, 25 and 100 HepG2 Si Particle size (nm): 10, 25, 50, 100 Concentration (μg/mL): 1, 5, 25 HUVECs QDs MTT Shape: Spherical Flow cytometry Composition: MPA and PEG Particle size (nm): ≈ 20 Zeta potential (mV) in buffer: ≈ 20 Concentration (nM): 20, 30, 35, 40, 50, 60, 75, and 100 (PEG) and 80, 90, 100, 110, 125, 150, 175, and 200 (MPA) Labrador-Rached et al. (2018) At dosages of 25 μg/mL or less, no toxicity was identified. However, at the high exposure concentration an approximate 25% cytotoxic response transpired The Pt nanoparticles induced ROS production in a dose-dependent fashion, with a substantial response associated with the 25 μg/mL condition Citrate-coated, 70-nm Pt nanoparticles were able to activate a significant stress response in HepG2 liver cells, even in the absence of cytotoxicity Zhou et al. (2019) At the administrative concentrations (1, 5, 25 μg/mL), all the four sizes of Si nanoparticles could induce an increase of both DNA damages and MN frequencies in culture, with a positive dose- and negative size-dependent effect relationship (S100 < S50 < S25 < S10) Si nanoparticles significantly enhanced levels of intracellular ROS, but decreased levels of GSH The levels of Nrf2 protein were significantly enhanced Peynshaert et al. (2017) PEGylated QDs induce cytotoxicity and oxidative stress, MPA-coated QDs are non-toxic up to 200 nM and reduce oxidative stress PEGylated QDs are easily taken up at low concentrations though uptake reaches a maximum around 40 nM. MPA-coated QDs are taken up proportionally with increasing dosage, though are only taken up efficiently at higher concentrations PEGylated QDs induce lysosomal impairment, while MPA-coated cause lysosomal activation Comet assay MN ROS GSH GFP-LC3 HeLa References Environmental Chemistry Letters Cells Nanoparticles Physicochemical characterizations Concentration (μg/mL): 0.1, 1, 10, 50 C60 SWCNT Fe3O4 and 100 BET surface area (m2/g): 10.58 (C60), 808.3 (SWCNT), 40.89 (Fe3O4) Average hydrodynamic diameter (nm): 142.0 (C60), 112.9 (SWCNT), 316.6 (Fe3O4) Zeta potential (mV): − 37.4 ± 6.45 (C60), 12.9 ± 3.19 (SWCNT), − 18.4 ± 4.49 (Fe3O4) Particle size (nm): 36.64 (C60), 9.00 (SWCNT diameter), 28.33 (Fe3O4) Co3O4 Fe2O3 The hydrodynamic diameter (nm) in water: 96.4 ± 0.57 (Co3O4), SiO2 74.6 ± 0.6 (Fe2O3), 41.7 ± 2.6 (SiO2), Al2O3 and 90.2 ± 2.4 (Al2O3) Shape: spherical Particle size (nm): 35.8 ± 0.8 (Co3O4), 43.7 ± 4.7 (Fe2O3), 17.1 ± 2.1 (SiO2), and 39.4 ± 3.9 (Al2O3) Concentration (μg/mL): 10, 25, 50, 75 and 100 Toxicity assays Cells Results References MTT LDH Fluorescence hPDLFs mDFs MTT, LDH, ROS, Comet assay Human lymphocytes Donmez Gungunes et al. (2017) All three nanoparticles caused loss of membrane integrity in time, in a gradually increasing manner In the 6 h of exposure, all three nanoparticles triggered the formation of ROS in both hPDLF and mDF cells mDF cells were more sensitive to C60, SWCNT and Fe3O4 nanoparticles exposure compared to hPDLF cells, which exhibited signs of cellular adaptation at nanoparticle exposures of lower concentrations Co3O4 nanoparticles showed decrease Rajiv et al. (2016) in cellular viability at doses of 50, 75, and 100 mg/ml and increase in cell membrane damage followed by Fe2O3, SiO2, and Al2O3 nanoparticles in a dose-dependent manner after 24 h of exposure to human lymphocytes The oxidative stress was evidenced in human lymphocytes by the induction of reactive oxygen species, lipid peroxidation, and depletion of catalase, reduced glutathione, and superoxide dismutase The Al2O3 nanoparticles showed the least DNA damage when compared with all the other nanoparticles Chromosomal aberration was observed at 100 mg/ml when exposed to Co3O4 nanoparticles and Fe2O3 nanoparticles The cytotoxicity and oxidative stress lead to DNA damage and chromosomal aberrations in human lymphocytes Environmental Chemistry Letters Table 3 (continued) 13 13 Table 3 (continued) Nanoparticles Physicochemical characterizations Toxicity assays Cells Results References PLGA-based Mean diameter (nm) in water: 200–230 (PLGA/PVA, PLGA/CS, PLGA/PF68),170 (PLGA stabilizerfree) 170–230 (DY700-PLGA, DY700PLGA/PVA, DY700-PLGA/CS, DY700-PLGA/PF68) Zeta potential (nm): 200–230 (PLGA/ PVA, PLGA/CS, PLGA/PF68), 170 (PLGA stabilizer-free), 170–230 (DY700-PLGA, DY700-PLGA/ PVA, DY700-PLGA/CS, DY700PLGA/PF68) Concentration (mg/mL): 0.01, 0.1, 1, and 10 Shape: spherical and monodisperse MTT Apoptosis/necrosis Cytokine secretion H2DCFHDA THP-1 All tested nanoparticles showed no or Grabowski et al. (2015) scarce signs of toxicity at therapeutically relevant concentrations (up to 0.1 mg/mL) At high concentrations (above 1 mg/ mL), cytotoxicity was found to be induced by the presence of stabilizers While stabilizer-free PLGA nanoparticles exerted no cytotoxicity, the slightly cytotoxic CS polymer conferred PLGA nanoparticles significant cytotoxicity when used as nanoparticles stabilizer; more surprisingly, the otherwise innocuous PVA and PF68 polymers also conferred a significant cytotoxicity to PLGA nanoparticles 143B: human bone osteosarcoma; Ag: silver; Al2O3: aluminum oxide; Au: gold; BEAS-2B: human bronchial epithelium cell line; CAT: catalase; CHSE-214: chinook salmon cells; Co: cobalt; Co(OH)2: cobalt hydroxide; Co3(PO4)2: cobalt phosphate; Co3O4: cobalt oxide; GSH: glutathione; GST: glutathione sulfotransferase; HaCaT: human keratinocyte cell; hFOB 1.19: human fetal osteoblast cell line; LDH: lactate dehydrogenase; LPO: lipid peroxidation; MG-63: human bone osteosarcoma cell line; MTT: mitochondria functioning; NR: Neutral-red uptake; SOD: superoxide dismutase; TiO2: titanium dioxide; WST-1: cell proliferation reagent; DCF-DA: dihydrodichlorofluorescein diacetate; DCFH-DA: dichlorodihydrofluorescein diacetate; GSH: glutathione; HepG2: human liver cell line; HGPRT: hypoxanthine–guanine phosphor ribosyl transferase; HUVECs: human umbilical vein endothelial cell line; IO: iron oxide; MN: micronucleus; MTS: CellTiter 96 AQueous One Solution Cell Proliferation; Nu/Nu strain: athymic nude mice; PEG: polyethylene glycol; PEI: polyethylenimine; Pt: platinum; RAW264.7: murine macrophages; ROS: reactive oxygen species; Si: silica; SKOV-3: human ovarian cancer cell line; V-79: Chinese hamster lung fibroblast cell line; ZnO: zinc oxide; Al2O3: aluminum oxide; C60: fullerene; Co3O4: cobalt (II, III) oxide; CS: chitosan; Fe2O3: iron (III) oxide; Fe3O4: iron oxide; GFP-LC3 HeLa: cervical epithelial cancer cell line HeLa; hPDLFs: human periodontal ligament fibroblasts; LDH: lactate dehydrogenase; mDFs: mouse dermal fibroblasts; MPA: 3-mercaptopropionic; PF68: poloxamer 188; PLGA: poly(lactide-co-glycolic); PVA: poly(vinyl alcohol); QDs: quantum dots; SiO2: silicon dioxide; SWCNT: single wall carbon nanotubes; THP-1: human monocyte-derived macrophages Environmental Chemistry Letters Environmental Chemistry Letters Fig. 3 Diseases associated with nanoparticles. Diseases linked to the inhaled nanoparticles include asthma, bronchitis, lung cancer, Parkinson’s and Alzheimer’s. Nanoparticles in the gastro-intestinal tract have been associated to Crohn’s disease and colon cancer. Nanoparticles that come into the circulatory system are linked to manifesta- tion of arteriosclerosis, thrombus and heart diseases, and eventually cardiac death. Moving to other organs, like liver and spleen, may cause to some other diseases of those organs. Exposure to some nanoparticles is correlated with the experience of autoimmune diseases. Adapted from Buzea et al. (2007) growth or reproduction, suggesting low toxicity. However, gold nanoparticles with positively charged coatings, such as branched polyethylenimine-coated gold nanoparticles or amine terminated (silicon and polystyrene nanoparticles), resulted in significant toxic effects in Caenorhabditis elegans. Additionally, Steckiewicz et al. (2019) showed that gold nanoparticles stars (≈ 215 nm) with the highest anticancer potential were the most cytotoxic type of tested nanoparticles, whereas gold nanoparticles spheres (≈ 6.3 nm) which appear to be the safest one with small anticancer potential. Additionally, short-term exposure to gold nanoparticles may not be toxic to cell growth, while long-term exposure may disturb cellular metabolism as well as energy homeostasis. Cellular uptake can occur with gold nanoparticles, and they can stay in endosomes/lysosomes or rely upon their surface functionalization into nuclei. Gold nanoparticles uptake relies on functionalization as well as cell type. If the gold nanoparticles are taken up by a healthy cell, then it will be eliminated eventually, whereas if it is taken up by a cancer cell, then the result will be cell death (Thota and Crans 2018). et al. 2015; Guo et al. 2018; Pulit-Prociak et al. 2014). Even though the increased use of silver nanoparticles provides many advantages in biomedical applications, their toxicological effects have explored. Silver nanoparticles can enter the body in different ways and accumulate in different tissues and organs, and passing the blood–brain barrier and eventually reaching the brain (Ciucă et al. 2017). Compared with other nanosized metals, silver nanoparticles show greater toxicity regarding the enhanced synthesis of ROS and leakage of the enzyme lactate dehydrogenase (Dasgupta and Ramalingam 2016; Foldbjerg et al. 2011; Haase et al. 2011). The toxicity of silver nanoparticles was reported to be dependent on many factors, including physical and chemical properties of silver nanoparticle, environmental conditions and contact interactions (Guo et al. 2018). Chen et al. (2015) examined the size-dependent toxicity of silver nanoparticles using three different characteristic sizes (15, 50 nm and 100 nm) against fish red blood cells. The smallest sized silver nanoparticle displayed a greater ability to induce hemolysis and membrane damage than particles of other sizes. Another toxicological study on silver nanoparticles revealed polyvinylpyrrolidone-coated silver nanoparticles on bacteria, viruses, microalgae, fungi and human and animal cells (including cancer cell lines) via a variety of viability and toxicological assays. It was discovered that biological systems from different taxonomies were inhibited with a concentration of silver nanoparticles at a similar magnitude (Vazquez-Muñoz et al. 2017). Silver Antibacterial, antifungal, antiviral and antifilarial properties of silver nanoparticles lead to use of these particles for biomedical purposes such as antimicrobial agents, drug delivery, molecular imaging, biomedical sensing and even cancer photodynamic therapy (Cameron et al. 2018; Chen 13 Environmental Chemistry Letters Nonetheless, Mulenos et al. (2020) showed the relatively low toxicity of silver nanoparticles based on the fact that only minutes amounts of silver ions, of 6.9 μg/mL, are released in oxic conditions, and 0.2 μg/mL under anoxic conditions, both levels being much lower to that of natural conditions. Indeed, toxicity is induced and controlled by production of ions. They found similar data for copper and titania. Cobalt Cobalt-based nanoparticles are used in pigments, catalysts, sensors, magnetic contrast agents and in energy storage devices (Cappellini et al. 2018). Exposure to cobalt or cobalt-containing nanoparticles was found to induce oxidative stress, DNA damage, morphological transformation and inflammatory responses in different cell types (Annangi et al. 2015; Wan et al. 2012, 2017). In addition, two cobaltcontaining substances, cobalt sulfate and cobalt-tungsten carbide, are listed as reasonably anticipated to be human carcinogens in the report on carcinogens based on sufficient evidence from experimental studies (NTP 2016). The potential toxicity of cobalt-based nanoparticles has been studied previously using different in vivo and in vitro models. Chattopadhyay et al. (2015), for example, evaluated the intracellular signaling transduction pathways involved in cobalt oxide nanoparticles mediated oxidative stress. It was found that bare cobalt oxide nanoparticles induced cell death significantly generated by ROS, which induced tumor necrosis factor alpha. This tumor necrosis factor alpha serves as an important function in cell death by activating caspase-8 followed by p38 MAPK and caspase-3. This study also revealed that bare cobalt oxide nanoparticles create a toxic effect on the human immune cell. Wan et al. (2017) explored the genotoxic effects of cobalt nanoparticles in vivo by using guanine phosphoribosyltransferase delta transgenic mice. They have shown that exposure to cobalt nanoparticles caused oxidative stress, lung inflammation and injury, and cell proliferation, which further resulted in DNA damage and mutation. Cappellini et al. (2018) also showed cellular uptake of three different cobalt-based nanoparticles in lung cells and induction of DNA strand breaks and oxidative damage by cobalt metal and cobalt (II) oxide nanoparticles. Aluminum oxide The Global Market for aluminum oxide nanoparticles reported that aluminum-based nanoparticles contribute to 20% of all nanosized chemicals (Future Markets 2013). They have found a wide range of applications in many sectors as paints, polymers, coatings, textiles, fuel cells, solar energy, airbag propellants and energetic materials because of its high hardness and mechanical strength (Kim et al. 2010; 13 Poborilova et al. 2013). There is evidence that exposure of aluminum oxide nanoparticles may lead to reduce cell viability, increase oxidative stress, mitochondrial dysfunction and alter proteins expression of blood–brain barrier (Alshatwi et al. 2012; Kim et al. 2010; Pakrashi et al. 2011; Yu et al. 2011; Zhang et al. 2011). Di Virgilio et al. (2010) observed dose-dependent cytotoxicity at lower concentrations (5 µg/mL) in Chinese hamster ovary cells treated with titanium oxide and aluminum oxide nanoparticles after 24 h by changes in lysosomal and mitochondrial dehydrogenase activity. They also reported genotoxic effects by micronucleus frequencies, which significantly increased at 0.5 and 1 µg/mL titanium oxide and 0.5–10 µg/mL aluminum oxide nanoparticles. Moreover, Srikanth et al. (2015) revealed that aluminum oxide nanoparticles induce cytotoxicity and membrane damage in Chinook salmon cells that may be mediated through morphological abnormalities, lipid peroxidation and oxidative stress. Titanium dioxide Titanium dioxide is one of the most increasingly manufactured nanoparticles and is listed in the top five nanoparticles in consumer products (Gea et al. 2019). They have been widely used in consumer products (sunscreens, cosmetics, toothpaste, pharmaceuticals, paints, plastics, self-cleaning devices and food additives) and industrial and medical applications because of their stronger catalytic activity (Shi et al. 2013; Ursini et al. 2014; Weir et al. 2012; Yin et al. 2012). The cytotoxicity and genotoxicity potential of titanium oxide nanoparticles has been investigated both in vitro and in vivo studies; however, the toxicological data are conflicting (Ranjan and Ramalingam 2016). Some studies in the literature observed no or low toxic effects (Ammendolia et al. 2017; Di Bucchianico et al. 2017); on the contrary, other studies have reported that titanium dioxide nanoparticles induce, cytotoxic, genotoxic and oxidative effects through oxidants generation, inflammation and apoptosis (Proquin et al. 2017; Rizk et al. 2017; Shi et al. 2010; Ursini et al. 2014; Yin et al. 2012). According to the International Agency for Research on Cancer, titanium dioxide nanoparticles are categorized as a possible carcinogen to humans (IARC 2010). The National Institute of Occupational Safety and Health also recommends exposure limits of 2.4 mg/m3 for fine titanium dioxide and 0.3 mg/m3 for ultrafine titanium dioxide (NIOSH 2011). The phototoxicity of titanium dioxide nanoparticles with four different sizes (< 25 nm, 31 nm, < 100 nm and 325 nm) and two crystal forms (anatase and rutile) toward human skin keratinocytes under ultraviolet radiation was evaluated by Yin et al. (2012). According to their results, ROS are generated by the ultraviolet radiation of all titanium dioxide nanoparticles (anatase and/or mixed anatase/rutile). Moreover, smaller titanium dioxide nanoparticles resulted in higher Environmental Chemistry Letters phototoxicity than larger particles. In another study, Proquin et al. (2017) showed food-grade titanium dioxide is cytotoxic in human colon carcinoma cell at a lower concentration than the nano-sized titanium dioxide particles and micro-sized titanium dioxide particles. However, food-grade titanium dioxide has no toxic effects in human colon adenocarcinoma cells cultures at concentrations up to 100 μg/cm2. Gea et al. (2019) evaluated the cytotoxicity, lactate dehydrogenase release and genotoxicity of three engineered titanium dioxide nanoparticles with different shapes (bipyramids, rods, platelets) in comparison with two commercial titanium dioxide nanoparticles (P25, food grade). Results showed that the cytotoxicity was overall low and was influenced by the nanoparticles shape as well as by light exposure. Besides, no significant lactate dehydrogenase release was detected. Instead, genotoxicity seemed to be influenced by the cellular uptake and the aggregation tendency of titanium dioxide nanoparticles. Moreover, the presence of light enhanced the genotoxic effect of some nanoparticles, primarily increasing the oxidative stress. Petersen et al. (2014) demonstrated that DNA samples incubated in the dark for 24 h with titanium dioxide nanoparticles (0.5–50 μg/mL) do not lead to the formation of oxidatively induced DNA damage. However, when the same samples are exposed to either visible light from 400 to 800 nm (energy dose of ~ 14.5 kJ/m) for 24 h or UVA light at 370 nm for 30 min (energy dose of~ 10 kJ/m2), there is a significant increase in oxidatively induced DNA damage at the 50 μg/mL dose for the visible light exposure and a significant increase in oxidatively induced DNA damage at the 5 μg/mL and 50 μg/mL doses for the UVA light exposure. Moreover, Xin et al. (2019) explored the interactive impacts of nano-TiO2 and triclosan on green alga Eremosphaera viridis under visible light using Lake Erie water. Platinum Even if platinum nanoparticles have proven to be excellent therapeutic agents in medicine for the treatment of cancer cells, they seem to produce undesirable side effects (Azmi and Shad 2017). In one in vitro study, Bendale et al. (2017) examined the cytotoxic effect of platinum nanoparticles on human lung adenocarcinoma, ovarian teratocarcinoma, pancreatic cancer cells and normal peripheral blood mononucleocyte cells and evaluated anticancer potential through induction of apoptosis on ovarian teratocarcinoma cells. They found that platinum nanoparticles exerted a cytotoxic effect on cancer cell lines, whereas no cytotoxic effect was observed at the highest dose on normal cells. The results showed that platinum nanoparticles had potent anticancer activities against ovarian teratocarcinoma cell line via induction of apoptosis and cell cycle arrest. A dose-dependent cytotoxicity of platinum nanoparticles was also investigated by Labrador-Rached et al. (2018). Findings revealed that a high platinum nanoparticles dosage induced cytotoxicity of human liver cell. However, low-level exposure to platinum nanoparticles was able to elicit multiple stress responses, secretion of proinflammatory cytokines and modulation of insulin-like growth factor-1-dependent signal transduction. Nevertheless, Gatto et al. (2018) have shown that citratecoated platinum nanoparticles are non-toxic and immunecompatible with monocytes cells. They also observed platinum nanoparticle-mediated ROS reduction and discovered their ability to modulate gene transcription without alteration of inflammatory cytokine release. Konieczny et al. (2013) found platinum nanoparticles trigger toxic effects on primary keratinocytes, decreasing cell metabolism, but these changes have no effects on cell viability or migration. Moreover, smaller nanoparticles exhibited more deleterious effect on DNA stability and higher caspases activation than the big ones. Samadi et al. (2018) exposed human ovarian cancer cells to platinum nanoparticles for 24 h at varying concentrations (0–50 μg/ml) to assess the toxicity of platinum nanoparticles on living cells. They observed no changes in neither cellular oxidative stress nor apoptotic or necrotic cell death. Zinc oxide Higher chemical activity, extremely strong oxidation and corrosion resistance, photocatalysis, unique stronger absorption and shielding ability to the ultraviolet rays properties of zinc oxide nanoparticles enable to the use of these nanoparticles in a broad range of application including catalysis, paints, wave filters, UV detectors, transparent conductive films, varistors, gas sensors, solar cells, sunscreens and cosmetic products (Guan et al. 2012; Huang et al. 2010; Subramaniam et al. 2019). Because of zinc oxide nanoparticle’s wide application in cosmetics and daily care products, both its exposure and toxicity to humans have increased (Senapati and Kumar 2018). De Berardis et al. (2010) evaluated the physical properties and the toxicological effects of zinc oxide nanoparticles. They showed a significant decrease in cell viability, remarkable morphological changes, apoptosis induction via ROS production and IL-8 release after treatment with zinc oxide nanoparticles (5 μg/cm2) for 24 h on human colon carcinoma cells. Besides, higher concentrations (10, 20 and 40 μg/cm2) induced about 98% cytotoxicity, with a cell survival lower than 5%, already after 24 h of treatment. Guan et al. (2012) also demonstrated that zinc oxide nanoparticles cause morphological changes, cytotoxicity and oxidative stress to human hepatocyte and human embryonic kidney cells. They have also observed the DNAdamaging effects for which lipid peroxidation and oxidative stress may be attributed as the probable causes. Similarly, Jain et al. (2019) revealed that zinc oxide nanoparticles induce oxidative stress, which leads to genotoxic insult, and 13 Environmental Chemistry Letters hypoxanthine-guanine phosphor ribosyl transferase gene mutation and later on cellular apoptosis in Chinese hamster lung fibroblast cells. Ng et al. (2017) investigated the toxicological profiles of zinc oxide nanoparticles in human lung fibroblasts in vitro and in vivo models employing the fruit fly Drosophila melanogaster. For in vitro toxicity, the results showed that there was a significant release of extracellular lactate dehydrogenase and decreased cell viability in zinc oxide nanoparticlestreated lung cells, indicating cellular damage and cytotoxicity. Production of ROS was seen to be identified with the critical articulation of DNA damage-inducible transcript and endoplasmic reticulum to nucleus signaling one gene, which is stress-associated. Oxidative stress-induced DNA damage was defined by the release of a DNA oxidation product and 8-hydroxydeoxyguanosine. Considering the in vivo study of the fruit fly D. melanogaster, substantial toxicity was detected in F1 progenies based on the intake of zinc oxide nanoparticles, which actuated noteworthy diminishing in the egg-to-adult suitability of the flies. This study recommended that zinc oxide nanoparticles induce a significant oxidative stress associated with cytotoxicity and genotoxicity in human lung fibroblasts in vitro and in D. melanogaster in vivo. Xiao et al. (2016) indicated that zinc oxide nanoparticles induced kidney toxicity via oxidative stress, which accompanied with the elevated level of ROS, malondialdehyde and decreased the level of superoxide dismutase in vitro and in vivo. Iron oxide Iron oxide nanoparticles have been widely used for biomedical applications including drug delivery, magnetic resonance imaging, thermal ablation therapy, in vivo cell tracking and magnetic separation of cells or molecules fields due to their superparamagnetic properties (Feng et al. 2018; Naqvi et al. 2010). In addition, high specific surface area and high reactivity of nanoscale zero-valent iron (nZVI) particles lead to the use of these particles in environmental remediation (Schmid et al. 2015). As an environmental remediation using nanofluid prepared by iron(II, III) oxide significantly increased CO2 absorption from the water (Arshadi et al. 2019). CO2 absorption mechanism was explained under the grazing (Fig. 4a), and hydrodynamic effect (Fig. 4b). The grazing effect is related to the absorption of gas molecules with methods of the nanoparticle surfaces at the bubble interface and afterward removing the adsorbed gas components from the nanoparticles surface into the fluid. Hydrodynamic effect of the nanoparticles encompassing the bubbles break the diffusion boundary layer which prompts a thinner viable layer. Gas diffusion into the liquid film increments by the presence of the particles near the interface between the bubble and the liquid which enhances 13 Fig. 4 Absorption mechanism in nanofluidic systems: a grazing effect or shuttle where the shuttle effect arises through the transport process of gas by nanoparticles in the small-scale liquid and b hydrodynamic effect in which the nanoparticles encircling the bubbles break the diffusion boundary layer and then make it thinner. Adapted from Zhang et al. (2018) the turbulence of the flow and the mass transfer coefficient. CO2 absorption by nanofluids was found to be dependent on many factors including type, size, particle and gas concentration, temperature, flow rates of gas and liquid. Besides the iron oxide nanoparticles, copper oxide, aluminum oxide, magnesium oxide, silicon dioxide, titanium dioxide, carbon nanotube and multiwalled carbon nanotube were used for CO2 absorption (Zhang et al. 2018). Additionally, nano zero-valent iron (Fe0) has been used effectively for remediation of contaminants in soil and ground water. Zero-valent iron is a reducing agent that reacts with dissolved oxygen, water and contaminants such as chlorinated ethenes, chlorinated methanes, brominated methanes, trihalomethanes, other polychlorinated hydrocarbon pesticides, as well as dyes (Petersen et al. 2012; Sarathy et al. 2008). Inhalation of iron oxide nanoparticles was found to cause oxidative stress by accumulating in the liver, spleen, lungs and brain with high ROS, which resulted in inflammation, low cell viability, cell lysis and disturbance of the blood coagulation system (Tan et al. 2018). The most of the studies investigated size and surface coating-dependent effects of iron oxide nanoparticles; for example, Naqvi et al. (2010) analyzed the dose- and time-dependent toxicity of Environmental Chemistry Letters superparamagnetic iron oxide nanoparticles with a mean size of 30 nm coated with Tween 80 surfactant on murine macrophage cells. Low concentrations of iron oxide nanoparticles (25–200 µg/mL for a two-hour exposure) have found to exhibit greater cell toxicity than higher concentrations (300–500 µg/mL for a six-hour exposure). Nevertheless, after seven days of incubation, dextran-coated iron oxide nanoparticles (100–150 nm, 0.1 mg/mL) reduced the cell viability in human macrophages, about 20%. Other researchers, Magdolenova et al. (2015) investigated the potential cytotoxicity and genotoxicity of uncoated and oleate-coated iron oxide nanoparticles on human lymphoblastoid cells and primary peripheral lymphocytes in vitro. Uncoated iron oxide nanoparticles were found not to be cytotoxic or genotoxic, while oleate-coated iron oxide nanoparticles were found to be cytotoxic in a dose-dependent manner and also induce DNA damage, indicating genotoxic potential. Moreover, Sadeghi et al. (2015) have studied the toxicity of iron oxide nanoparticle on human hepatoma cells. Results showed an increase of the oxidative damage leads cells to the apoptosis and therefore reduced cell viability after 12-h and 24-h exposure to 25, 50, 75 and 100 µg/ml of iron oxide nanoparticle. Feng et al. (2018) investigated the influence of particle size and surface coating on the biological distribution of iron oxide nanoparticles and their biological effects in vitro and in vivo. They demonstrated that both size and coating have a remarkable impact on the cellular uptake, cytotoxicity, distribution and clearance of iron oxide nanoparticles. Polyethylenimine-coated iron oxide nanoparticles have found to exhibit higher cellular uptake in both macrophages and cancer cells, severe cytotoxicity, faster clearance and less tumor distribution than polyethylene glycol-coated iron oxide nanoparticles. Besides, smallersized polyethylene glycol-coated iron oxide nanoparticles (10 nm) showed relatively higher cellular uptake and tumor accumulation than larger ones (30 nm). Non-metallic nanoparticles Silica Silica nanoparticles, also known as silicone dioxide, have attracted great attention because of their unique properties including large surface area-to-volume ratios, tunable pore size and connectivity, biocompatibility and ease of surface modification (Geranio et al. 2010; Kim et al. 2015).These properties make them appealing tools for biomedical and biotechnological fields, such as medical diagnostics, drug delivery, gene therapy, biomolecules detection, photodynamic therapy and bioimaging (Duan et al. 2013; Yu et al. 2014). Even though silica nanoparticle was thought to be vastly biocompatible material for use in biomedical and biotechnological applications, they could be accumulated and retained in the heart, liver, spleen, kidney and brain after ingestion, inhalation or skin application (Zhou et al. 2019). Recent studies have been also indicated that exposure to silica nanoparticles could induce ROS generation and cause oxidative stress (Athinarayanan et al. 2014; Duan et al. 2013; Zhou et al. 2019). Yu et al. (2014) investigated the effects and interaction mechanisms of ROS and autophagy triggered by silica nanoparticles. Autophagy and autophagic cell death were induced as a result of ROS generation in human heptacellular carcinoma cells after exposed to the silica nanoparticles. Wang et al. (2018) have reported that four sizes (10, 25, 50, 100 nm) of silica nanoparticles can cause apoptosis to human umbilical vein endothelial cells in culture. Genotoxic potentials of four sizes (10, 25, 50, 100 nm) of silica nanoparticle to human umbilical vein endothelial cells in culture have determined by Zhou et al. (2019). The results showed that exposure to silica nanoparticles could induce a significant increase of both DNA damage and cytokinesis-block micronucleus frequencies in human umbilical vein endothelial cells. Additionally, increased levels of ROS decreased levels of reduced glutathione, and enhanced levels of erythroid 2-related factor 2 protein were observed in the silica nanoparticles-treated human umbilical vein endothelial cells. Quantum dots The optical fluorescent property of quantum dots can be conjugated by bioactive moieties to target specific biological events and cellular structures, such as labeling neoplastic cells, DNA and cell membrane receptors (Liu et al. 2015). The toxicity of quantum dots relies on many factors, mainly the result of individual quantum dots physicochemical properties and environmental settings: size, concentration, charge, outer coating bioactivity. Also, oxidative, photolytic and mechanical stability appear to be decisive factors for quantum dots toxicity. According to Havrdova et al. (2016), significant differences were found in the toxicity of sulfide quantum dots depending on their surface charge. Polyethyleneglycol-modified dots with neutral charge did not induce any abnormalities in cell morphology, intracellular trafficking, and cell cycle up to concentrations of 300 μg/ mL. Pristine carbon dots with negative charge arrested the G2/M phase of the cell cycle, stimulated proliferation and led to higher oxidative stress; however, they did not enter the cell nucleus. In contrast, positively charged polyethylenimine-coated dots were found to be the most cytotoxic, entered into the nucleus and induced the largest changes in the G0/G1 phase of the cell cycle, even at concentrations of around 100 μg/mL. In another research, exposure to cadmium sulfide quantum dots at low concentrations was induced only minor damage to nuclear DNA and none to mitochondrial DNA. However, the stress caused an increase 13 Environmental Chemistry Letters in the production of ROS, which triggered the mitochondriamediated intrinsic apoptotic pathway involving a cascade of transcriptomic events, finally prompting the activation of a rescue pathway (Bali et al. 2020; Paesano et al. 2016). Peynshaert et al. (2017) reported that 3-mercaptopropioniccoated quantum dots are highly biocompatible, where the lysosomal activation and ROS reductions were induced by these quantum dots, and likely rescue the cell from potentially nanomaterial-induced toxic effects. However, polyethylene glycol-coated quantum dots exhibited significant toxicity owing to their capacity to induce ROS production and autophagy malfunction through lysosomal impairment. Fullerene Non-functionalized fullerenes can be highly distributed in all tissues, and indicated a long-lasting buildup, which has been observed in bones, spleen, liver and kidney (Bahadar et al. 2016; Sergio et al. 2013). An in vitro and in vivo study of fullerene nanoparticle toxicity was explored by several researchers. As demonstrated by in vitro study, exposure to C70 fullerene for 24 h at a concentration of 25.2 µg/mL led to the induction of intracellular ROS level in human keratinocyte and lung carcinoma cells (Horie et al. 2013). Shipelin et al. (2015) have investigated the effect of fullerene dispersion on iliac mucosa and liver at doses of 0.1, 1.0 and 10 mg/ kg body weight over 92 days in vivo. Fullerene found to be toxic to the hepatic tissue at the highest examined doses of 10 mg/kg body weight. However, in another study, no significant cytotoxicity was observed upon 24 h exposure to fullerene derivatives at less than 50 µg/mL. Higher concentration (> 100 µg/mL) of fullerene derivatives with different surface modification found to decrease the proliferation of macrophage cell and induced cytotoxicity through the apoptosis pathway (Xiang et al. 2012). Zhang et al. (2015) also reported that fullerene aggregates have no toxic effect at concentrations lower than 1.65 mg/L. However, fullerene aggregates induce cytotoxicity with the increase in concentration through the depletion of the mitochondrial membrane potential and the increase of intracellular ROS, triggering apoptosis of macrophage by activation of the mitochondrial pathway. Additionally, the benthic organism Chironomus riparius was exposed to C60 fullerene using the environmentally realistic method of allowing the fullerenes to settle down on the sediment surface (Waissi-Leinonen et al. 2012). According to light microscopic images, fullerene agglomerates were observed in the gut, but no absorption into the gut epithelial cells was detected. In the organisms exposed to fullerenes, microvilli were damaged and were significantly shorter. The potential toxicity of fullerene to Chironomus riparius appears to be caused by morphological changes, inhibiting larval growth. 13 Polymeric material Polymeric nanoparticles have been considered as excellent drug carriers in cancer theraphy due to their excellent pharmacokinetic properties such as drug loading, drug release, structure stability and nanoparticles degradation (Li et al. 2017). These nanoparticles can be also conjugated to or encapsulated in polymers to improve nanomedicine that offers sustained release and decent biocompatibility with cells and tissues (Bahadar et al. 2016). Additionally, most biodegradable polymeric nanoparticles are known to be nontoxic, non-inflammatory and non-immunologic, and they do not activate neutrophils (Kumari et al. 2010). Voigt et al. (2014) nanoparticles injected rhodamine-labeled polybutylcyanoacrylate nanoparticles variations into rats and monitored the survival and morphology of retrogradely labeled neurons by in vivo confocal neuroimaging for 5 weeks. They demonstrated that polybutylcyanoacrylate nanoparticles do not induce neuronal death in pharmacologically effective concentrations, even when coated with surfactants that are adverse to viability in cell cultures. They concluded that polybutylcyanoacrylate nanoparticles are a non-toxic tool for drug delivery into the central nervous system. On the contrary, it has been known that positively charged nanoparticles have been shown to be toxic to many different cell types (Elliott et al. 2017). Grabowski et al. (2015) evaluated the toxicity of poly(lactide-co-glycolic)-based nanoparticles (stabilizer-free or associated with stabilizers) on human-like THP-1 macrophages. At concentrations below 0.1 mg/mL, poly(lactide-co-glycolic)-based nanoparticles showed few signs of toxicity, either in mitochondrial activity, induction of apoptosis/necrosis or production of intracellular ROS and secretions of pro-inflammatory cytokines. At high concentrations (above 1 mg/mL), cytotoxicity was found to be higher with the presence of stabilizers, whereas the stabilizer-free poly(lactide-co-glycolic)-based nanoparticles showed no cytotoxicity. Therefore, surface coating can significantly affect the cytotoxicity of nanoparticles by changing their physicochemical properties and can drastically alter the pharmacokinetics, distribution, accumulation and toxicity of nanoparticles (Gatoo et al. 2014). Conclusion Improvement in nanotechnology has been viewed as one of the original bearings in current technological advancements in many industrial fields. Nevertheless, the danger of contaminating the earth and the conceivable adverse effects on human health must be taken into consideration. In summary, the discussion here has focused on the toxicity and behavior of various classes of nanoparticles in the environment. Based on previous studies, these nanoparticles were found to be Environmental Chemistry Letters toxic; however, the reason for their toxicity is undetermined. There is still an unclear relationship between nanoparticles and their surroundings. As a future work, more investigations are expected to assess the safety of complex multi-part and functional nanomaterials, and researchers should create validated models equipped of release, transport, transformation, accumulation, as well as uptake of engineered nanomaterials in the environment. These models ought to relate physical and chemical attributes of nanomaterials to their manner, enable a coordinated way to deal with potential effect of engineered nanomaterials and nanoproducts, and predict impacts in subjected population. Also, carrying out research on nanotechnology risks and advantages outside the scientific community is difficult and, however, is fundamental for dialogs dependent on the sound science. This implies creating communication exercises that empower fundamental data to be summarized, investigated and eventually incorporated for different invested individuals, including decision makers and buyers. At last, a worldwide understanding of nanotechnology-explicit risks is basic if big and small ventures are to work on a level playing field and creating economies on structuring safe nanotechnologies. Regardless of evolvement reviewed here, many research obstacles within the area must be addressed. 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