Nanotoxicity and Mechanisms

Nanotechnology has already contributed prominently in diverse scientific avenues and the scope is expanding progressively. The nanomaterial (NM) repository is also prospering rapidly, propelled by the extensive demand for nanomedicine to combat emerging situations such as viral outbreaks or antimicrobial resistance and to provide solution to decades old problems like cancer along with other potential applications in wound healing, fracture management, nano-vaccines, advanced imaging and diagnostics, etc. Consequently, the load of nanoparticles (NPs) on the ecosystem is increasing rapidly, enhancing the probability of NM exposure to all the living organisms via diverse routes. Several NMs such as metallic and metal oxide NPs, carbon-based NMs, silica-based NMs, polymeric or composite NMs, quantum dots, etc. have found to inflict toxicity by diverse mechanisms that include but not limited to generation of oxidative stress by overproduction of free radicals and depletion of cellular antioxidants, inflammation by upregulating the secretion of pro-inflammatory cytokines, cell cycle alteration, affecting cell viability, inducing the formation of autophagosome and apoptosis by activating caspase-mediated pathways, alteration in transcriptional regulations, causing DNA damage and genotoxicity, etc. The toxicity signatures can either be manifested at molecular level or by phenotypic changes to the cellular architectures. Enumeration of different tissue- or organ-specific toxicity markers, cell viability assays and morphological examinations, quantifying different enzymatic and non-enzymatic antioxidants, measuring lipid peroxidation, evaluating the expression of different cytokines and transcription factors, monitoring DNA damage and oxidation products along with histological examination are usually performed to elucidate the nanotoxicological implications. Two-dimensional monolayer cell culture is the most commonly employed in-vitro model for nanotoxicity evaluation, however, it lacks the barrier function, thus, often overestimates the toxic effects. So, three-dimensional cultures, organoids, spheroids, organ-on-chip models are gaining in popularity as alternative in-vitro models to provide findings close to the in vivo models. Different laboratory animals, particularly rats and mice are the most extensively used in vivo models, but again the species-specific anatomical and physiological variations can influence the ultimate nanotoxicity outcome. Although the significance of a nanotoxicity study is being realized progressively, the stakeholders are still predominantly focused on customizing novel engineered NMs rather than on toxicity analysis. In addition, existing nanotoxicity studies are mostly on short-term basis and on a single testing model, however, the long-term effects has remained neglected. No international standards for nanotoxicity study are currently available and the reproducibility is also a major issue. So, formation of a consortium to study toxicological effects of different NPs is urgently needed along with the establishment of a central databank for NM study that may help to develop predictive models for enumerating toxicological consequences of present and emerging nanomaterials.