Tailoring metal oxide nanozymes for biomedical applications: trends, limitations, and perceptions.

Nanomaterials with enzyme-like properties are known as 'nanozymes'. Nanozymes are preferred over natural enzymes due to their nanoscale characteristics and ease of tailoring of their physicochemical properties such as size, structure, composition, surface chemistry, crystal planes, oxygen vacancy, and surface valence state. Interestingly, nanozymes can be precisely controlled to improve their catalytic ability, stability, and specificity which is unattainable by natural enzymes. Therefore, tailor-made nanozymes are being favored over natural enzymes for a range of potential applications and better prospects. In this context, metal oxide nanoparticles with nanozyme-mimicking characteristics are exclusively being used in biomedical sectors and opening new avenues for future nanomedicine. Realising the importance of this emerging area, here, we discuss the mechanistic actions of metal oxide nanozymes along with their key characteristics which affect their enzymatic actions. Further, in this critical review, the recent progress towards the development of point-of-care (POC) diagnostic devices, cancer therapy, drug delivery, advanced antimicrobials/antibiofilm, dental caries, neurodegenerative diseases, and wound healing potential of metal oxide nanozymes is deliberated. The advantages of employing metal oxide nanozymes, their potential limitations in terms of nanotoxicity, and possible prospects for biomedical applications are also discussed with future recommendations.

Unravelling the toxicity of carbon nanomaterials - From cellular interactions to mechanistic understanding.

The application of carbon nanomaterials in diverse fields has substantially increased their demand for commercial usage. Within the earliest decade, the development of functional materials has further increased the significance of this element. Despite the advancements recorded, the potential harmful impacts of embracing carbon nanomaterials for biological applications must be balanced against their advantages. Interestingly, many studies have neglected the intriguing and dynamic cellular interaction of carbon nanomaterials and the mechanistic understanding of their property-driven behaviour, even though common toxicity profiles have been reported. Reiterating the toxicity issue, several researchers conclude that these materials have minimal toxicity and may be safe for contact with biological systems at certain dosages. Here, we aim to provide a report on the significance of some of the properties that influence their toxicity. After that, a description of the implication of nanotoxicology in humans and living systems, revealing piece by piece their exposure routes and possible risks, will be provided. Then, an extensive discussion of the mechanistic puzzle modulating the interface between various human cellular systems and carbon nanomaterials such as carbon nanotubes, carbon dots, graphene, fullerenes, and nanodiamonds will follow. Finally, this review also sheds light on the organization that handles the risk associated with nanomaterials.

Polystyrene nanoplastics induce lipophagy via the AMPK/ULK1 pathway and block lipophagic flux leading to lipid accumulation in hepatocytes.

Micro- and nanoplastic pollution has emerged as a significant global concern due to their extensive presence in the environment and potential adverse effects on human health. Nanoplastics can enter the human circulatory system and accumulate in the liver, disrupting hepatic metabolism and causing hepatotoxicity. However, the precise mechanism remains uncertain. Lipophagy is an alternative mechanism of lipid metabolism involving autophagy. This study aims to explore how polystyrene nanoplastics (PSNPs) influence lipid metabolism in hepatocytes via lipophagy. Initially, it was found that PSNPs were internalized by human hepatocytes, resulting in decreased cell viability. PSNPs were found to induce the accumulation of lipid droplets (LDs), with autophagy inhibition exacerbating this accumulation. Then, PSNPs were proved to activate lipophagy by recruiting LDs into autophagosomes and block the lipophagic flux by impairing lysosomal function, inhibiting LD degradation. Ultimately, PSNPs were shown to activate lipophagy through the AMPK/ULK1 pathway, and knocking down AMPK exacerbated lipid accumulation in hepatocytes. Overall, these results indicated that PSNPs triggered lipophagy via the AMPK/ULK1 pathway and blocked lipophagic flux, leading to lipid accumulation in hepatocytes. Thus, this study identifies a novel mechanism underlying nanoplastic-induced lipid accumulation, providing a foundation for the toxicity study and risk assessments of nanoplastics.

Melanin for Photoprotection and Hair Coloration in the Emerging Era of Nanocosmetics.

Nanotechnology is revolutionizing fields of high social and economic impact. such as human health preservation, energy conversion and storage, environmental decontamination, and art restoration. However, the possible global-scale application of nanomaterials is raising increasing concerns, mostly related to the possible toxicity of materials at the nanoscale. The possibility of using nanomaterials in cosmetics, and hence in products aimed to be applied directly to the human body, even just externally, is strongly debated. Preoccupation arises especially from the consideration that nanomaterials are mostly of synthetic origin, and hence are often seen as "artificial" and their effects as unpredictable. Melanin, in this framework, is a unique material since in nature it plays important roles that specific cosmetics are aimed to cover, such as photoprotection and hair and skin coloration. Moreover, melanin is mostly present in nature in the form of nanoparticles, as is clearly observable in the ink of some animals, like cuttlefish. Moreover, artificial melanin nanoparticles share the same high biocompatibility of the natural ones and the same unique chemical and photochemical properties. Melanin is hence a natural nanocosmetic agent, but its actual application in cosmetics is still under development, also because of regulatory issues. Here, we critically discuss the most recent examples of the application of natural and biomimetic melanin to cosmetics and highlight the requirements and future steps that would improve melanin-based cosmetics in the view of future applications in the everyday market.

Immunomodulatory effects of single and combined exposure to ZnO and TiO2 nanoparticles on rainbow trout challenged with Aeromonas salmonicida achromogenes.

The increasing release of engineered nanoparticles (ENPs) in aquatic ecosystems stresses the need for stringent investigations of nanoparticle mixture toxicity towards aquatic organisms. Here, the individual and combined immunotoxicity of two of the most consumed ENPs, the ZnO and the TiO2 ones, was investigated on rainbow trout juveniles (Oncorhynchus mykiss). Fish were exposed to environmentally realistic concentrations (21 and 210 µg L-1 for the ZnO and 210 µg L-1 for the TiO2) for 28 days, and then challenged with the pathogenic bacterium, Aeromonas salmonicida achromogenes. Antioxidant and innate immune markers were assessed before and after the bacterial infection. None of the experimental conditions affected the basal activity of the studied innate immune markers and the redox balance. However, following the bacterial infection, the expression of genes coding for pro and anti-inflammatory cytokines (il1ß and il10), as well as innate immune compounds (mpo) were significantly reduced in fish exposed to the mixture. Conversely, exposure to ZnO NPs alone seemed to stimulate the immune response by enhancing the expression of the IgM and c3 genes for instance. Overall, our results suggest that even though the tested ENPs at their environmental concentration do not strongly affect basal immune functions, their mixture may alter the development of the immune response when the organism is exposed to a pathogen by interfering with the inflammatory response.

Antibacterial Action of Zn2+ Ions Driven by the In Vivo Formed ZnO Nanoparticles.

Antibacterial formulations based on zinc oxide nanoparticles (ZnO NPs) are widely used for antibiotic replacement in veterinary medicine and animal nutrition. However, the undesired environmental impact of ZnO NPs triggers a search for alternative, environmentally safer solutions. Here, we show that Zn2+ in its ionic form is a more eco-friendly antibacterial, and its biocidal action rivals that of ZnO NPs (<100 nm size), with a minimal biocidal concentration being 41(82) µg mL-1 vs 5 µg mL-1 of ZnO NPs, as determined for 103(106) CFU mL-1 E. coli. We demonstrate that the biocidal activity of Zn2+ ions is primarily associated with their uptake by E. coli and spontaneous in vivo transformation into insoluble ZnO nanocomposites at an internal bacterial pH of 7.7. Formed in vivo nanocomposite then damages E. coli membrane and intracellular components from the inside, by forming insoluble biocomposites, whose formation can also trigger ZnO characteristic reactions damaging the cells (e.g., by generation of high-potential reactive oxygen species). Our study defines a special route in which Zn2+ metal ions induce the death of bacterial cells, which might be common to other metal ions capable of forming semiconductor oxides and insoluble hydroxides at a slightly alkaline intracellular pH of some bacteria.

Effects of Multiple Stressors, Pristine or Sulfidized Silver Nanomaterials, and a Pathogen on a Model Soil Nematode Caenorhabditis elegans.

Previous research using the model soil nematode Caenorhabditis elegans has revealed that silver nanoparticles (AgNP) and their transformed counterpart, sulfidized AgNP (sAgNP), reduce their reproduction and survival. To expand our understanding of the environmental consequences of released NP, we examined the synergistic/antagonistic effects of AgNP and sAgNP along with AgNO3 (ionic control) on C. elegans infected with the pathogen Klebsiella pneumoniae. Individual exposures to each stressor significantly decreased nematode reproduction compared to controls. Combined exposures to equitoxic EC30 concentrations of two stressors, Ag in nanoparticulate (AgNP or sAgNP) or ionic form and the pathogen K. pneumoniae, showed a decline in the reproduction that was not significantly different compared to individual exposures of each of the stressors. The lack of enhanced toxicity after simultaneous combined exposure is partially due to Ag decreasing K. pneumoniae pathogenicity by inhibiting biofilm production outside the nematode and significantly reducing viable pathogens inside the host. Taken together, our results indicate that by hindering the ability of K. pneumoniae to colonize the nematode's intestine, Ag reduces K. pneumoniae pathogenicity regardless of Ag form. These results differ from our previous research where simultaneous exposure to zinc oxide (ZnO) NP and K. pneumoniae led to a reproduction level that was not significantly different from the controls.

The toxicity of superparamagnetic iron oxide nanoparticles induced on the testicular cells: In vitro study.

Superparamagnetic iron oxide nanoparticles (SPIONs) have gained significant attention in biomedical research due to their potential applications. However, little is known about their impact and toxicity on testicular cells. To address this issue, we conducted an in vitro study using primary mouse testicular cells, testis fragments, and sperm to investigate the cytotoxic effects of sodium citrate-coated SPIONs (Cit_SPIONs). Herein, we synthesized and physiochemically characterized the Cit_SPIONs and observed that the sodium citrate diminished the size and improved the stability of nanoparticles in solution during the experimental time. The sodium citrate (measured by thermogravimetry) was biocompatible with testicular cells at the used concentration (3%). Despite these favorable physicochemical properties, the in vitro experiments demonstrated the cytotoxicity of Cit_SPIONs, particularly towards testicular somatic cells and sperm cells. Transmission electron microscopy analysis confirmed that Leydig cells preferentially internalized Cit_SPIONs in the organotypic culture system, which resulted in alterations in their cytoplasmic size. Additionally, we found that Cit_SPIONs exposure had detrimental effects on various parameters of sperm cells, including motility, viability, DNA integrity, mitochondrial activity, lipid peroxidation (LPO), and ROS production. Our findings suggest that testicular somatic cells and sperm cells are highly sensitive and vulnerable to Cit_SPIONs and induced oxidative stress. This study emphasizes the potential toxicity of SPIONs, indicating significant threats to the male reproductive system. Our findings highlight the need for detailed development of iron oxide nanoparticles to enhance reproductive nanosafety.

Integrating Explicit and Implicit Fullerene Models into UNRES Force Field for Protein Interaction Studies.

Fullerenes, particularly C60, exhibit unique properties that make them promising candidates for various applications, including drug delivery and nanomedicine. However, their interactions with biomolecules, especially proteins, remain not fully understood. This study implements both explicit and implicit C60 models into the UNRES coarse-grained force field, enabling the investigation of fullerene-protein interactions without the need for restraints to stabilize protein structures. The UNRES force field offers computational efficiency, allowing for longer timescale simulations while maintaining accuracy. Five model proteins were studied: FK506 binding protein, HIV-1 protease, intestinal fatty acid binding protein, PCB-binding protein, and hen egg-white lysozyme. Molecular dynamics simulations were performed with and without C60 to assess protein stability and investigate the impact of fullerene interactions. Analysis of contact probabilities reveals distinct interaction patterns for each protein. FK506 binding protein (1FKF) shows specific binding sites, while intestinal fatty acid binding protein (1ICN) and uteroglobin (1UTR) exhibit more generalized interactions. The explicit C60 model shows good agreement with all-atom simulations in predicting protein flexibility, the position of C60 in the binding pocket, and the estimation of effective binding energies. The integration of explicit and implicit C60 models into the UNRES force field, coupled with recent advances in coarse-grained modeling and multiscale approaches, provides a powerful framework for investigating protein-nanoparticle interactions at biologically relevant scales without the need to use restraints stabilizing the protein, thus allowing for large conformational changes to occur. These computational tools, in synergy with experimental techniques, can aid in understanding the mechanisms and consequences of nanoparticle-biomolecule interactions, guiding the design of nanomaterials for biomedical applications.

Emerging trends and future challenges of advanced 2D nanomaterials for combating bacterial resistance.

The number of multi-drug-resistant bacteria has increased over the last few decades, which has caused a detrimental impact on public health worldwide. In resolving antibiotic resistance development among different bacterial communities, new antimicrobial agents and nanoparticle-based strategies need to be designed foreseeing the slow discovery of new functioning antibiotics. Advanced research studies have revealed the significant disinfection potential of two-dimensional nanomaterials (2D NMs) to be severed as effective antibacterial agents due to their unique physicochemical properties. This review covers the current research progress of 2D NMs-based antibacterial strategies based on an inclusive explanation of 2D NMs' impact as antibacterial agents, including a detailed introduction to each possible well-known antibacterial mechanism. The impact of the physicochemical properties of 2D NMs on their antibacterial activities has been deliberated while explaining the toxic effects of 2D NMs and discussing their biomedical significance, dysbiosis, and cellular nanotoxicity. Adding to the challenges, we also discussed the major issues regarding the current quality and availability of nanotoxicity data. However, smart advancements are required to fabricate biocompatible 2D antibacterial NMs and exploit their potential to combat bacterial resistance clinically.

Ecotoxicity of doped zinc oxide nanoparticles: Perspectives on environmental safety.

Studies on the ecotoxicity of doped zinc oxide nanoparticles (ZnO NPs) are recent, with the first publications starting in 2010. In this sense, this is the first study that comprehensively reviews the ecotoxicological effects of ZnO NPs doped with lanthanide elements to fill this literature gap. This research explores a multifaceted question at the intersection of nanotechnology, toxicology, and environmental science. Different types of dopants commonly used for ZnO doping were investigated in this review, focusing on the ecotoxicological effects of lanthanides as dopants. Bacteria were the main class of organisms used in ecotoxicological studies, since antimicrobial activity of these nanomaterials is extensively explored to combat the imminent problem of resistant bacteria, in addition to enabling the safe use of these nanomaterials for biomedical applications. Doping appears to exhibit greater efficacy when compared to undoped ZnO NPs in terms of antimicrobial effects; however, it cannot be said that it has no impact on non-target organisms. An extensive examination of the literature also establishes the importance and need to evaluate the effects of doped ZnO NPs on organisms from different environmental compartments in order to identify their potential impacts. We underscore the dearth of research information regarding the environmental toxicity/ecotoxicity of doped ZnO nanoparticles across various ecological levels, thereby limiting the extrapolation of findings to humans or other complex models. Therefore, we emphasize the urgency of a multi-parameter assessment for the development of sanitary and environmentally safe nanotechnologies.

Tellurium and Nano-Tellurium: Medicine or Poison?

Tellurium (Te) is the heaviest stable chalcogen and is a rare element in Earth's crust (one to five ppb). It was discovered in gold ore from mines in Kleinschlatten near the present-day city of Zlatna, Romania. Industrial and other applications of Te focus on its inorganic forms. Tellurium can be toxic to animals and humans at low doses. Chronic tellurium poisoning endangers the kidney, liver, and nervous system. However, Te can be effective against bacteria and is able to destroy cancer cells. Tellurium can also be used to develop redox modulators and enzyme inhibitors. Soluble salts that contain Te had a role as therapeutic and antimicrobial agents before the advent of antibiotics. The pharmaceutical use of Te is not widespread due to the narrow margin between beneficial and toxic doses, but there are differences between the measure of toxicity based on the Te form. Nano-tellurium (Te-NPs) has several applications: it can act as an adsorptive agent to remove pollutants, and it can be used in antibacterial coating, photo-catalysis for the degradation of dyes, and conductive electronic materials. Nano-sized Te particles are the most promising and can be produced in both chemical and biological ways. Safety assessments are essential to determine the potential risks and benefits of using Te compounds in various applications. Future challenges and directions in developing nano-materials, nano-alloys, and nano-structures based on Te are still open to debate.

Lipidomics Analysis Unravels Aberrant Lipid Species and Pathways Induced by Zinc Oxide Nanoparticles in Kidney Cells.

Zinc oxide nanoparticles (ZnO NPs) are widely used in versatile applications, from high technology to household products. While numerous studies have examined the toxic gene profile of ZnO NPs across various tissues, the specific lipid species associated with adverse effects and potential biomarkers remain elusive. In this study, we conducted a liquid chromatography-mass spectrometry based lipidomics analysis to uncover potential lipid biomarkers in human kidney cells following treatment with ZnO NPs. Furthermore, we employed lipid pathway enrichment analysis (LIPEA) to elucidate altered lipid-related signaling pathways. Our results demonstrate that ZnO NPs induce cytotoxicity in renal epithelial cells and modulate lipid species; we identified 64 lipids with a fold change (FC) > 2 and p < 0.01 with corrected p < 0.05 in HK2 cells post-treatment with ZnO NPs. Notably, the altered lipids between control HK2 cells and those treated with ZnO NPs were associated with the sphingolipid, autophagy, and glycerophospholipid pathways. This study unveils novel potential lipid biomarkers of ZnO NP nanotoxicity, representing the first lipidomic profiling of ZnO NPs in human renal epithelial cells.

Nanomaterials in biology and medicine: a new perspective on its toxicity and applications.

Nanotechnology offers excellent prospects for application in biology and medicine. It is used for detecting biological molecules, imaging, and as therapeutic agents. Due to nano-size (1-100 nm) and high surface-to-volume ratio, nanomaterials possess highly specific and distinct characteristics in the biological environment. Recently, the use of nanomaterials as sensors, theranostic, and drug delivery agents has become popular. The safety of these materials is being questioned because of their biological toxicity, such as inflammatory responses, cardiotoxicity, cytotoxicity, inhalation problems, etc., which can have a negative impact on the environment. This review paper focuses primarily on the toxicological effects of nanomaterials along with the mechanisms involved in cell interactions and the generation of reactive oxygen species by nanoparticles, which is the fundamental source of nanotoxicity. We also emphasize the greener synthesis of nanomaterials in biomedicine, as it is non-hazardous, feasible, and economical. The review articles shed light on the complexities of nanotoxicology in biosystems and the environment.

Hemocompatibility studies in nanotoxicology: Hemolysis or eryptosis? (A review).

Hemocompatibility evaluation is an important step in nanotoxicological studies. It is generally accepted that nanomaterials promote lysis of erythrocytes, blood clotting, alter phagocytosis, and upregulate pro-inflammatory cytokines. However, there are no standardized guidelines for testing nanomaterials hemocompatibility despite the fact that nanomaterials enter the bloodstream and interact with blood cells. In this review, the current knowledge on the ability of nanomaterials to induce distinct cell death modalities of erythrocytes is highlighted primarily focusing on hemolysis and eryptosis. This review aims to summarize the molecular mechanisms underlying erythrotoxicity of nanomaterials and critically compare the sensitivity and efficiency of hemolysis or eryptosis assays for nanomaterials blood compatibility testing. The list of eryptosis-inducing nanomaterials is growing, but it is still difficult to generalize how physico-chemical properties of nanoparticles affect eryptosis degree and molecular mechanisms involved. Thus, another aim of this review is to raise the awareness of eryptosis as a nanotoxicological tool to encourage the corresponding studies. It is worthwhile to consider adding eryptosis to in vitro nanomaterials hemocompatibility testing protocols and guidelines.

Plant-nano interactions: A new insight of nano-phytotoxicity.

Whether nanoparticles (NPs) are boon or bane for society has been a centre of in-depth debate and key consideration in recent times. Exclusive physicochemical properties like small size, large surface area-to-volume ratio, robust catalytic activity, immense surface energy, magnetism and superior biocompatibility make NPs obligatory in many scientific, biomedical and industrial ventures. Nano-enabled products are newer entrants in the present era. To attenuate environmental stress and maximize crop yields, scientists are tempted to introduce NPs as augmented supplements in agriculture. The feasible approaches for NPs delivery are irrigation, foliar spraying or seed priming. Internalization of excessive NPs to plants endorses negative implications at higher trophic levels via biomagnification. The characteristics of NPs (dimensions, type, solubility, surface charge), applied concentration and duration of exposure are prime factors conferring nanotoxicity in plants. Several reports approved NPs persuaded toxicity can precisely mimic abiotic stress effects. The signature effects of nanotoxicity include poor root outgrowth, biomass reduction, oxidative stress evolution, lipid peroxidation, biomolecular damage, perturbed antioxidants, genotoxicity and nutrient imbalance in plants. NPs stress impels mitogen-activated protein kinase signaling cascade and urges stress responsive defence gene expression to counteract stress in plants. Exogenous supplementation of nitric oxide (NO), arbuscular mycorrhizal fungus (AMF), phytohormones, and melatonin (ME) is novel strategy to circumvent nanotoxicity. Briefly, this review appraises plants' physio-biochemical responses and adaptation scenarios to endure NPs stress. As NPs stress represents large-scale contaminants, advanced research is indispensable to avert indiscriminate NPs usage for synchronizing nano-security in multinational markets.

Non-invasive methods of monitoring Fe3O4 magnetic nanoparticle toxicity in human liver HepaRG cells using impedance biosensing and Coherent anti-Stokes Raman spectroscopic (CARS) microscopy.

Functionalized nanoparticles have been developed for use in nanomedicines for treating life threatening diseases including various cancers. To ensure safe use of these new nanoscale reagents, various assays for biocompatibility or cytotoxicity in vitro using cell lines often serve as preliminary assessments prior to in vivo animal testing. However, many of these assays were designed for soluble, colourless materials and may not be suitable for coloured, non-transparent nanoparticles. Moreover, cell lines are not always representative of mammalian organs in vivo. In this work, we use non-invasive impedance sensing methods with organotypic human liver HepaRG cells as a model to test the toxicity of PEG-Fe3O4 magnetic nanoparticles. We also use Coherent anti-Stokes Raman Spectroscopic (CARS) microscopy to monitor the formation of lipid droplets as a parameter to the adverse effect on the HepaRG cell model. The results were also compared with two commercial testing kits (PrestoBlue and ATP) for cytotoxicity. The results suggested that the HepaRG cell model can be a more realistic model than commercial cell lines while use of impedance monitoring of Fe3O4 nanoparticles circumventing the uncertainties due to colour assays. These methods can play important roles for scientists driving towards the 3Rs principle - Replacement, Reduction and Refinement.

Special Issue: Agricultural Nanotechnology.

Agricultural nanotechnology has considerable promise for addressing global agricultural production/security, biodiversity, and global warming issues. Current trends in publications and patents demonstrate that biotechnology technologies, particularly for crops, are being developed to improve agricultural productivity and disease management. In the current issue, we strongly advocate for the use of biosynthesized nanoparticles from a variety of sources, including plants, agricultural waste, and microbes, as a prerequisite for significant and in-depth study. Nanomaterials offer a wide range of practical uses in agriculture, including nanofertilizers, nanopesticides, nanoherbicides, nanosensors, and smart delivery systems for controlled agrochemical release. Additionally, nano-tools are employed for plant breeding and genetic manipulation. A thorough examination of the physicochemical soil properties of the agricultural fields where nanoparticles will be used will aid in minimizing their impact on plant and soil biota. Finally, and most importantly, we strongly recommend the inclusion of nanotoxicity, legislation, biosafety, and risk assessment as the top priorities when developing regulatory policies to address biosafety concerns. Starting today, thorough efforts must be carried out to advance and develop futuristic work based on recognized knowledge shortages.

Nanoparticles-mediated entomotoxicology: lessons from biologica.

Nanotechnology has grown in importance in medicine, manufacturing, and consumer products. Nanoparticles (NPs) are also widely used in the field of insect pest management, where they show a variety of toxicological effects on insects. As a result, the primary goal of this review is to compile and evaluate available information on effects of NPs on insects, by use of a timely, bibliometric analysis. We also discussed the manufacturing capacity of NPs from insect tissues and the toxic effects of NPs on insects. To do so, we searched the Web of Science database for literature from 1995 to 2023 and ran bibliometric analyses with CiteSpace© and Bibliometrix©. The analyses covered 614 journals and identified 1763 relevant documents. We found that accumulation of NPs was one of the top trending topics. China, India, and USA had the most published papers. The most overall reported models of insects were those of Aedes aegypti (yellow fever mosquito), Culex quinquefasciatus (southern house mosquito), Bombyx mori (silk moth), and Anopheles stephensi (Asian malaria mosquito). The application and methods of fabrication of NPs using insect tissues, as well as the mechanism of toxicity of NPs on insects, were also reported. A uniform legal framework is required to allow nanotechnology to fully realize its potential while minimizing harm to living organisms and reducing the release of toxic metalloid nanoparticles into the environment.

Genotoxic and neurotoxic potential of intracellular nanoplastics: A review.

Plastic waste comprises polymers of different chemicals that disintegrate into nanoplastic particles (NPLs) of 1-100-nm size, thereby littering the environment and posing a threat to wildlife and human health. Research on NPL contamination has up to now focused on the ecotoxicology effects of the pollution rather than the health risks. This review aimed to speculate about the possible properties of carcinogenic and neurotoxic NPL as pollutants. Given their low-dimensional size and high surface size ratio, NPLs can easily penetrate biological membranes to cause functional and structural damage in cells. Once inside the cell, NPLs can interrupt the autophagy flux of cellular debris, alter proteostasis, provoke mitochondrial dysfunctions, and induce endoplasmic reticulum stress. Harmful metabolic and biological processes induced by NPLs include oxidative stress (OS), ROS generation, and pro-inflammatory reactions. Depending on the cell cycle status, NPLs may direct DNA damage, tumorigenesis, and lately carcinogenesis in tissues with high self-renewal capabilities like epithelia. In cells able to live the longest like neurons, NPLs could trigger neurodegeneration by promoting toxic proteinaceous aggregates, OS, and chronic inflammation. NPL genotoxicity and neurotoxicity are discussed based on the gathered evidence, when available, within the context of the intracellular uptake of these newcomer nanoparticles. In summary, this review explains how the risk evaluation of NPL pollution for human health may benefit from accurately monitoring NPL toxicokinetics and toxicodynamics at the intracellular resolution level.