Effects of silver and gold nanoparticles of different sizes in human pulmonary fibroblasts

Abstract

Silver and gold nanoparticles (Ag–AuNPs) are currently some of the most manufactured nanomaterials. Accordingly, the hazards associated with human exposure to Ag–AuNPs should be investigated to facilitate the risk assessment process. In particular, because pulmonary exposure to Ag–AuNPs occurs during handling of these nanoparticles, it is necessary to evaluate the toxic response in pulmonary cells. The aim of this study was to evaluate the in vitro mechanisms of toxicity of different sizes of silver (4.7 and 42?nm) and gold nanoparticles (30, 50 and 90?nm) in human pulmonary fibroblasts (HPF). The toxicity was evaluated by observing cell viability and oxidative stress parameters. Data showed that AgNPs-induced cytotoxicity was size-dependent, whereas the AuNPs of the three sizes showed similar cytotoxicity. Silver nanoparticles of 4.7?nm were much more toxic than the large silver nanoparticles and the AuNPs. However, the pre-treatment with the antioxidant, N-acetyl-l-cysteine, protected HPF cells against treatment with Ag–AuNPs. The oxidative stress parameters revealed significant increase in reactive oxygen species levels, depletion of glutathione level and slight, but not statistically significant inactivation of superoxide dismutase, suggesting generation of oxidative stress. Hence, care has to be taken while processing and formulating the Ag–AuNPs till their final finished product.     

Assessment of the toxicity of silver nanoparticles in vitro: A mitochondrial perspective

The major toxicological concern associated with nanomaterials is the fact that some manufactured nanomaterials are redox active, and some particles transport across cell membranes, especially into mitochondria. Thus, evaluation of their toxicity upon acute exposure is essential. In this work, we evaluated the toxicity of silver nanoparticles (40 and 80 nm) and their effects in rat liver mitochondria bioenergetics.Wistar rat liver mitochondria demonstrate alterations in respiration and membrane potential capacities in the presence of either 40 or 80 nm silver nanoparticles. Our data demonstrated a statistically significant decrease in mitochondrial membrane potential, ADP-induced depolarization, and respiratory control ratio (RCR) upon exposure to silver nanoparticles.Our results show that silver nanoparticles cause impairment of mitochondrial function, due mainly to alterations of mitochondrial membrane permeability. This results in an uncoupling effect on the oxidative phosphorylation system. Thus, mitochondrial toxicity may have a central role in the toxicity resulting from exposure to silver nanoparticles.     

Exposure to silver nanoparticles induces size- and dose-dependent oxidative stress and cytotoxicity in human colon carcinoma cells

The antimicrobial properties of silver nanoparticles (AgNPs) have made these particles one of the most frequently utilized nanomaterials in consumer products; therefore, a comprehensive understanding of their toxicity is necessary. In particular, information about the cellular uptake and size dependence of AgNPs is insufficient.In this study, we evaluated the size-dependent effects of AgNPs by treating the human LoVo cell line, an intestinal epithelium model, with spherical AgNPs of well-defined sizes (10, 20, 40, 60 and 100 nm). The cellular uptake was visualized by confocal laser scanning microscopy, and various cytotoxicity parameters were analyzed in a size- and dose-dependent manner. In addition, the cellular proteomic response to 20 and 100 nm AgNPs was investigated to increase the understanding of potential mechanisms of action. Our data indicated that cellular uptake and toxicity were regulated by size; smaller particles easily penetrated the cells, and 100 nm particles did not. It was hypothesized that this size-dependent effect resulted from the stimulation of a signaling cascade that generated ROS and inflammatory markers, leading to mitochondrial dysfunction and subsequently inducing apoptosis. By contrast, the cell proliferation, was independent of AgNPs particle size, indicating a differentially regulated, ROS-independent pathway.     

Evaluation of cytotoxic,oxidative stress,proinflammatory and genotoxic effect of silver nanoparticles in human lung epithelial cells

Silver nanoparticles are increasingly used in various products, due to their antibacterial properties. Despite its wide spread use, only little information on possible adverse health effects exists. Therefore, the aim of this study was to assess the toxic potential of silver nanoparticles (<100 nm) in human lung epithelial (A549) cells and the underlying mechanism of its cellular toxicity. Silver nanoparticles induced dose and time‐dependent cytotoxicity in A549 cells demonstrated by MTT and LDH assays. Silver nanoparticles were also found to induce oxidative stress in dose and time‐dependent manner indicated by depletion of GSH and induction of ROS, LPO, SOD, and catalase. Further, the activities of caspases and the level of proinflammatory cytokines, namely interleukin‐1β (IL‐1β) and interleukin‐6 (IL‐6) were significantly higher in treated cells. DNA damage, as measured by single cell gel electrophoresis, was also dose and time‐dependent signicants in A549 cells. This study investigating the effects of silver nanoparticles in human lung epithelial cells has provided valuable insights into the mechanism of potential toxicity induced by silver nanoparticles and warrants more careful assessment of silver nanoparticles before their industrial applications. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 149–160, 2015.     

Comparison of acute to chronic ratios between silver and gold nanoparticles,using Ceriodaphnia dubia

As integration of nanoparticles (NPs) into products becomes more common, the need to address the paucity of chronic hazard information for aquatic environments required to determine risk potential increases. This study generated acute and chronic toxicity reference values for Ceriodaphnia dubia exposed to 20 and 100?nm silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) to generate and evaluate potential differences in acute-to-chronic ratios (ACR) using two different feeding methods. A modified feeding procedure was employed alongside the standard procedures to investigate the influence of food on organism exposure. An 8-h period before food was added allowed direct organism exposure to NP dispersions (and associated ions) without food-to-NP interactions. The AgNPs [chronic lethal median concentrations (LC50) between 18.7 and 31.9?µg/L] were substantially more toxic than AuNPs (LC50?=?21 507 to >26 384?µg/L). The modified chronic testing method resulted in greater sensitivity in AgNPs exposures. However, the modified feeding ration had less of an effect in exposures to the larger (100?nm) AgNPs compared to smaller particles (20?nm). The ACRs for AgNPs using the standard feeding ration were 1.6 and 3.5 for 20?nm and 100?nm, respectively. The ACRs for AgNPs using the modified feeding ration were 3.4 and 7.6 for 20?nm and 100?nm NPs, respectively. This supports that the addition of the standard feeding ration decreases C. dubia chronic sensitivity to AgNPs, although it must also be recognized organisms may be sensitized due to less access to food. The ACRs for 20?nm and 100?nm AuNPs (standard ration only) were 4.0 and 3.0, respectively. It is important to also consider that dissolved Ag⁺ ions are more toxic than AgNPs, based on both acute toxicity values in the cited literature and chronic toxicity thresholds generated in this study that support existing thresholds that Ag⁺ are likely protective of AgNPs effects.     

Impact of silver nanoparticles on human cells: Effect of particle size

Abstract

This work investigated the cytotoxicities of three silver nanoparticles (SNPs) SNP-5, SNP-20 and SNP-50 with different sizes (～ 5 nm, ～ 20 nm and ～ 50 nm) using four human cell models (A549, SGC-7901, HepG2 and MCF-7). Endpoints included cell morphology, cell viability, cellular membrane integrity, oxidative stress and cell cycle progression. Observable deleterious effects on the cell morphologies and membrane integrity were induced by SNP-5 and SNP-20. SNPs elevated the ROS levels in cells and arrested the cells at S phase. Apoptosis occurred for 4–9% of the exposed cells. All these cellular responses as well as EC50 values were found to be size-dependent for the tested SNPs. Ultrastructural observations confirmed the presence of SNPs inside cells. Elemental analysis of silver in cells by ICP-MS showed that smaller nanoparticles enter cells more easily than larger ones, which may be the cause of higher toxic effects. The findings may assist in the design of SNP applications and provide insights into their toxicity.     

Both released silver ions and particulate Ag contribute to the toxicity of AgNPs to earthworm Eisenia fetida

Abstract

To disentangle the contribution of ionic and nanoparticulate Ag to the overall toxicity to the earthworm Eisenia fetida, a semi-permeable membrane strategy was used to separate Ag⁺ released from silver nanoparticles (AgNPs) in an aqueous exposure. Internal Ag fractionation, activities of antioxidant enzymes and metabolites in E. fetida were determined after 96?h of exposure to two sizes of polyvinylpyrrolidone-coated AgNPs. The response of the antioxidant system combined with the content of malondialdehyde indicated that the Ag⁺ released from AgNPs induced significant oxidative stress to the earthworms. Ag accumulated from AgNPs was predominantly associated with the granules and cell membrane compartments, whereas dissolved Ag was localized in the cytosol-containing fraction. In both Ag⁺ exposures, two intermediates in the Krebs cycle, succinate and fumarate, were significantly elevated and depleted, respectively. A similar alteration pattern was seen in groups exposed to both smaller AgNPs (S AgNP, 10?nm) and larger AgNP (L AgNP, 40?nm), indicating that these effects in E. fetida were induced by exposure to released Ag⁺. In addition, unique metabolic responses including decreased malate and glucose levels in S AgNP-exposed earthworms could be associated with exposure to nanoparticulate silver. Increased leucine and arginine and decreased ATP and inosine levels were observed in L AgNP exposures only, which clearly demonstrated a size-specific effect of AgNPs. Collectively, this study provided strong evidence that nanosilver acts by a different mechanism than ionic silver to cause acute toxicity to E. fetida, but further verification under different environmental conditions is needed.     

Comparative cytotoxicity of nanosilver in human liver HepG2 and colon Caco2 cells in culture

The use of silver nanoparticles in food, food contact materials, dietary supplements and cosmetics has increased significantly owing to their antibacterial and antifungal properties. As a consequence, the need for validated rapid screening methods to assess their toxicity is necessary to ensure consumer safety. This study evaluated two widely used in vitro cell culture models, human liver HepG2 cells and human colon Caco2 cells, as tools for assessing the potential cytotoxicity of food‐ and cosmetic‐related nanoparticles. The two cell culture models were utilized to compare the potential cytotoxicity of 20‐nm silver. The average size of the silver nanoparticle determined by our transmission electron microscopy (TEM) analysis was 20.4 nm. The dynamic light scattering (DLS) analysis showed no large agglomeration of the silver nanoparticles. The concentration of the 20‐nm silver solution determined by our inductively coupled plasma–mass spectrometry (ICP‐MS) analysis was 0.962 mg ml^–1. Our ICP‐MS and TEM analysis demonstrated the uptake of 20‐nm silver by both HepG2 and Caco2 cells. Cytotoxicity, determined by the Alamar Blue reduction assay, was evaluated in the nanosilver concentration range of 0.1 to 20 µg ml^–1. Significant concentration‐dependent cytotoxicity of the nanosilver in HepG2 cells was observed in the concentration range of 1 to 20 µg ml^–1 and at a higher concentration range of 10 to 20 µg ml^–1 in Caco2 cells compared with the vehicle control. A concentration‐dependent decrease in dsDNA content was observed in both cell types exposed to nanosilver but not controls, suggesting an increase in DNA damage. The DNA damage was observed in the concentration range of 1 to 20 µg ml^–1. Nanosilver‐exposed HepG2 and Caco2 cells showed no cellular oxidative stress, determined by the dichlorofluorescein assay, compared with the vehicle control in the concentration range used in this study. A concentration‐dependent decrease in mitochondria membrane potential in both nanosilver exposed cell types suggested increased mitochondria injury compared with the vehicle control. The mitochondrial injury in HepG2 cells was significant in the concentration range of 1 to 20 µg ml^–1, but in Caco2 cells it was significant at a higher concentration range of 10 to 20 µg ml^–1. These results indicated that HepG2 cells were more sensitive to nanosilver exposure than Caco2 cells. It is generally believed that cellular oxidative stress induces cytotoxicity of nanoparticles. However, in this study we did not detect any nanosilver‐induced oxidative stress in either cell type at the concentration range used in this study. Our results suggest that cellular oxidative stress did not play a major role in the observed cytotoxicity of nanosilver in HepG2 and Caco2 cells and that a different mechanism of nanosilver‐induced mitochondrial injury leads to the cytotoxicity. The HepG2 and Caco2 cells used this study appear to be targets for silver nanoparticles. The results of this study suggest that the differences in the mechanisms of toxicity induced by nanosilver may be largely as a consequence of the type of cells used. This differential rather than universal response of different cell types exposed to nanoparticles may play an important role in the mechanism of their toxicity. In summary, the results of this study indicate that the widely used in vitro models, HepG2 and Caco2 cells in culture, are excellent systems for screening cytotoxicity of silver nanoparticles. These long established cell culture models and simple assays used in this study can provide useful toxicity and mechanistic information that can help to better inform safety assessments of food‐ and cosmetic‐related silver nanoparticles. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.     

Apoptosis induction by silica nanoparticles mediated through reactive oxygen species in human liver cell line HepG2

Silica nanoparticles are increasingly utilized in various applications including agriculture and medicine. In vivo studies have shown that liver is one of the primary target organ of silica nanoparticles. However, possible mechanisms of hepatotoxicity caused by silica nanoparticles still remain unclear. In this study, we explored the reactive oxygen species (ROS) mediated apoptosis induced by well-characterized 14 nm silica nanoparticles in human liver cell line HepG2. Silica nanoparticles (25-200 μg/ml) induced a dose-dependent cytotoxicity in HepG2 cells. Silica nanoparticles were also found to induce oxidative stress in dose-dependent manner indicated by induction of ROS and lipid peroxidation and depletion of glutathione (GSH). Quantitative real-time PCR and immunoblotting results showed that both the mRNA and protein expressions of cell cycle checkpoint gene p53 and apoptotic genes (bax and caspase-3) were up-regulated while the anti-apoptotic gene bcl-2 was down-regulated in silica nanoparticles treated cells. Moreover, co-treatment of ROS scavenger vitamin C significantly attenuated the modulation of apoptotic markers along with the preservation of cell viability caused by silica nanoparticles. Our data demonstrated that silica nanoparticles induced apoptosis in human liver cells, which is ROS mediated and regulated through p53, bax/bcl-2 and caspase pathways. This study suggests that toxicity mechanisms of silica nanoparticles should be further investigated at in vivo level.     

Characterisation,cytotoxicity and apoptosis studies of methotrexate-loaded PLGA and PLGA-PEG nanoparticles

Abstract

Methotrexate (MTX) widely used in the treatments of various types of malignancies, but high toxicity and short plasma half-life have limited its use. This study was aimed at developing a polymeric drug delivery system for improving the therapeutic index of this potent drug. To achieve these goals, PLGA and PLGA-PEG nanoparticles were prepared using the emulsification-solvent diffusion technique and were optimized for particle size and entrapment efficiency. The optimum loaded nanoparticles were evaluated by cytotoxicity and their ability to induce apoptosis compared to free drug by examining of caspase-3 activity. The results showed that optimized particles were 182?±?14?nm and 258?±?10?nm in size for PLGA-PEG and PLGA nanoparticles, respectively, with an entrapment efficiency of more than 51%. The cytotoxicity experiment showed that the nanoparticles were more effective than pure MTX and increase the activity of caspase-3 in MCF7 and AGS and A549 cell lines.     

Effect of exposure time,particle size and uptake pathways in immune cell lysosomal cytotoxicity of mussels exposed to silver nanoparticles

Cytotoxicity evaluation of hemocytes (lysosomal membrane stability [LMS] assay) from Mytilus galloprovincialis Lamarck, exposed to a sublethal dose (100?μg/L) of two size of silver nanoparticles (AgNPs: <50?nm and <100?nm) – prior to and after inhibition of potential uptake pathways (i.e., clathrin- and caveolae-mediated endocytosis) within different times of exposure (3, 6, 12?h) – showed that there was a significant cytotoxic effect on immune cells of mussels exposed for different times to either AgNP size (p?p?相似文献   

The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion.

This investigation was designed to determine whether nano-sized manganese oxide (Mn-40 nm) particles would induce dopamine (DA) depletion in a cultured neuronal phenotype, PC-12 cells, similar to free ionic manganese (Mn(2+)). Cells were exposed to Mn-40 nm, Mn(2+) (acetate), or known cytotoxic silver nanoparticles (Ag-15 nm) for 24 h. Phase-contrast microscopy studies show that Mn-40 nm or Mn(2+) exposure did not greatly change morphology of PC-12 cells. However, Ag-15 nm and AgNO(3) produce cell shrinkage and irregular membrane borders compared to control cells. Further microscopic studies at higher resolution demonstrated that Mn-40 nm nanoparticles and agglomerates were effectively internalized by PC-12 cells. Mitochondrial reduction activity, a sensitive measure of particle and metal cytotoxicity, showed only moderate toxicity for Mn-40 nm compared to similar Ag-15 nm and Mn(2+) doses. Mn-40 nm and Mn(2+) dose dependently depleted DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), while Ag-15 nm only significantly reduced DA and DOPAC at concentrations of 50 mug/ml. Therefore, the DA depletion of Mn-40 nm was most similar to Mn(2+), which is known to induce concentration-dependent DA depletion. There was a significant increase (> 10-fold) in reactive oxygen species (ROS) with Mn-40 nm exposure, suggesting that increased ROS levels may participate in DA depletion. These results clearly demonstrate that nanoscale manganese can deplete DA, DOPAC, and HVA in a dose-dependent manner. Further study is required to evaluate the specific intracellular distribution of Mn-40 nm nanoparticles, metal dissolution rates in cells and cellular matrices, if DA depletion is induced in vivo, and the propensity of Mn nanoparticles to cross the blood-brain barrier or be selectively uptaken by nasal epithelium.     

Identification of the appropriate dose metric for pulmonary inflammation of silver nanoparticles in an inhalation toxicity study

A number of studies have shown that induction of pulmonary toxicity by nanoparticles of the same chemical composition depends on particle size, which is likely in part due to differences in lung deposition. Particle size mostly determines whether nanoparticles reach the alveoli, and where they might induce toxicity. For the risk assessment of nanomaterials, there is need for a suitable dose metric that accounts for differences in effects between different sized nanoparticles of the same chemical composition. The aim of the present study is to determine the most suitable dose metric to describe the effects of silver nanoparticles after short-term inhalation. Rats were exposed to different concentrations (ranging from 41 to 1105?µg silver/m³ air) of 18, 34, 60 and 160?nm silver particles for four consecutive days and sacrificed at 24?h and 7 days after exposure. We observed a concentration-dependent increase in pulmonary toxicity parameters like cell counts and pro-inflammatory cytokines in the bronchoalveolar lavage fluid. All results were analysed using the measured exposure concentrations in air, the measured internal dose in the lung and the estimated alveolar dose. In addition, we analysed the results based on mass, particle number and particle surface area. Our study indicates that using the particle surface area as a dose metric in the alveoli, the dose–response effects of the different silver particle sizes overlap for most pulmonary toxicity parameters. We conclude that the alveolar dose expressed as particle surface area is the most suitable dose metric to describe the toxicity of silver nanoparticles after inhalation.     

PLGA nanoparticles for intravitreal peptide delivery: statistical optimization,characterization and toxicity evaluation

Abstract

Frequent intravitreal injections are currently used to overcome the ocular barriers and provide sufficient drug to the posterior eye segment. However, intravitreal injections have been associated with a number of complications and high treatment costs. To overcome these limitations, peptide-loaded poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NPs) were developed using the nanoprecipitation technique and were optimized via Box–Behnken Design (BBD) and Response Surface Methodology (RSM). Developed NPs were evaluated for potential toxicity and cell apoptosis using the zebrafish embryo toxicity (ZET) model with titanium dioxide NPs and ethanol (1% v/v) serving as positive controls. Developed NPs had a size of 75.6–153.8?nm, a polydispersity index between 0.11 and 0.25 and a zeta potential of ?9.4 to ?46.0?mV. Loaded peptide was found to be stable under various experimental conditions tested. BBD and RSM were validated through the characterization of optimized formulations. Survival and hatching rates of NP-treated zebrafish 0–144?h post-fertilization were found to be normal with no significant malformations. Cellular apoptosis studies also endorsed the non-cytotoxic nature of the NPs. The overall results indicate that optimized PLGA nanoparticles could be a promising platform for efficient peptide delivery to the posterior segment of the eye.     

A comparative study of the toxicological aspects of vanadium pentoxide and vanadium oxide nanoparticles

Abstract

Indiscriminate use of vanadium oxide nanoparticles (NPs) in steel industries and their release during combustion of fossil fuels makes it essential to study their toxic potential. Herein, we assessed the toxicological effects of two types of in-house synthesized vanadium oxide NPs in Wistar rats exposed to NPs through inhalation route. V₂O₅ and VO₂ NPs exhibited rod and spherical symmetry, respectively with a mean diameter of 50?±?20 and 30?±?10?nm. Assessment of bronchoalveolar lavage fluid parameters demonstrated that VO₂ NP-exposed animals had higher levels of lactate dehydrogenase, gamma-glutamyl transpeptidase and alkaline phosphatase as compared to V₂O₅ NP-exposed animals. The levels of oxidative stress markers malondialdehyde and reduced glutathione also indicated higher toxic potential of VO₂ NPs. Moreover, after 7-day recovery, the levels of the above parameters were closer to normal levels only in V₂O₅-exposed animals. Interestingly, histopathological and immune-histopathology analysis (TNF-α) of lung tissue showed higher damage and inflammatory response in VO₂ NP-exposed animals, which persisted even after 7 days of recovery period. Surprisingly, the carcinogenic potential of vanadium oxide NPs came into light which was indicated by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay as well as the decreased levels of p53 and Bax, in lung tissue of NP-exposed animals. Notably, the physiochemical characterization of NPs, especially the shape and the size, play a central role in shaping the toxicity of these NPs and thus should be extensively evaluated for outlining the regulatory guidelines.     

Effects of particle size and coating on nanoscale Ag and TiO2 exposure in zebrafish (Danio rerio) embryos

Abstract

Manufactured metal (oxide) nanoparticles are entering the aquatic environment with little understanding on their potential health impacts for exposed organisms. Adopting an integrative approach, we investigated effects of particle size and coating on biological responses for two of the most commonly used metal (oxide) nanoscale particles, silver (Ag) and titanium dioxide (TiO₂) in zebrafish embryos. Titanium dioxide nanoparticles (nominally, 4 nm, 10 nm, 30 nm and 134 nm) had little or no toxicity on the endpoints measured. Ag both in nano form (10 nm and 35 nm) and its larger counterpart (600–1600 nm) induced dose-dependent lethality and morphological defects, occurring predominantly during gastrula stage. Of the silver material tested 10 nm nanoparticles appeared to be the most toxic. Coating Ag nanoparticles with citrate or fulvic acid decreased toxicity significantly. In situ hybridisation analysis identified the yolk syncytial layer (YSL) as a target tissue for Ag-nano toxicity where there was a significant induction of the heavy metal stress response gene, metallothionein 2 (Mt2) at sub-lethal exposures. Coherent Anti-stroke Raman Scattering (CARS) microscopy provided no evidence for silver particles crossing the chorionic membrane in exposed embryos. Collectively, our data suggest that silver ions play a major role in the toxicity of Ag nanoparticles.     

Genotoxicity evaluation of amorphous silica nanoparticles of different sizes using the micronucleus and the plasmid lacZ gene mutation assay

Abstract

We investigated the potential of four well-characterized amorphous silica nanoparticles to induce chromosomal aberrations and gene mutations using two in vitro genotoxicity assays. Transmission electron microscopy (TEM) was used to verify the manufacturer's nominal size of 10, 30, 80 and 400 nm which showed actual sizes of 11, 34, 34 and 248 nm, respectively. The 80 (34) nm silica nanoparticles induced chromosomal aberrations in the micronucleus assay using 3T3-L1 mouse fibroblasts and the 30 (34) and 80 (34) nm silica nanoparticles induced gene mutations in mouse embryonic fibroblasts carrying the lacZ reporter gene. TEM imaging demonstrated that the majority of nanoparticles were localized in vacuoles and not in the nucleus of 3T3-L1 cells, indicating that the observed DNA damage was most likely a result of indirect mechanisms. Further studies are needed to reveal these mechanisms and to determine the biological relevance of the effects of these particular silica nanoparticles in vivo.     

Toxic implications of silver nanoparticles on the central nervous system: A systematic literature review

Silver nanoparticles have many medical and commercial applications, but their effects on human health are poorly understood. They are used extensively in products of daily use, but little is known about their potential neurotoxic effects. A xenobiotic metal, silver, has no known physiological significance in the human body as a trace metal. Biokinetics of silver nanoparticles indicates its elimination from the body via urine and feces route. However, a substantial amount of evidence from both in vitro and in vivo experimental research unequivocally establish the fact of easier penetration of smaller nanoparticles across the blood–brain barrier to enter in brain and thereby interaction with cellular components to induce neurotoxic effects. Toxicological effects of silver nanoparticles rely on the degree of exposure, particle size, surface coating, and agglomeration state as well as the type of cell or organism used to evaluate its toxicity. This review covers pertinent facts and the present state of knowledge about the neurotoxicity of silver nanoparticles reviewing the impacts on oxidative stress, neuroinflammation, mitochondrial function, neurodegeneration, apoptosis, and necrosis. The effect of silver nanoparticles on the central nervous system is a topic of growing interest and concern that requires immediate consideration.