Abstract
Engineered nanomaterials are bestowed with certain inherent physicochemical properties unlike their parent materials, rendering them suitable for the multifaceted needs of state-of-the-art biomedical, and pharmaceutical applications. The log-phase development of nano-science along with improved “bench to beside” conversion carries an enhanced probability of human exposure with numerous nanoparticles. Thus, toxicity assessment of these novel nanoscale materials holds a key to ensuring the safety aspects or else the global biome will certainly face a debacle. The toxicity may span from health hazards due to direct exposure to indirect means through food chain contamination or environmental pollution, even causing genotoxicity. Multiple ways of nanotoxicity evaluation include several in vitro and in vivo methods, with in vitro methods occupying the bulk of the “experimental space.” The underlying reason may be multiple, but ethical constraints in in vivo animal experiments are a significant one. Two-dimensional (2D) monoculture is undoubtedly the most exploited in vitro method providing advantages in terms of cost-effectiveness, high throughput, and reproducibility. However, it often fails to mimic a tissue or organ which possesses a defined three-dimensional structure (3D) along with intercellular communication machinery. Instead, microtissues such as spheroids or organoids having a precise 3D architecture and proximate in vivo tissue-like behavior can provide a more realistic evaluation than 2D monocultures. Recent developments in microfluidics and bioreactor-based organoid synthesis have eased the difficulties to prosper nano-toxicological analysis in organoid models surpassing the obstacle of ethical issues. The present review will enlighten applications of organoids in nanotoxicological evaluation, their advantages, and prospects toward securing commonplace nano-interventions.
Highlights
Nanotechnology empowered by engineered nanomaterials has almost left no stone untouched in the scientific arena of the current century
Nanomaterials are ascribed with a nanoscale range external/internal structure at least in one dimension, which adorns them with distinct physicochemical properties unlike their bulk equivalents (Taniguchi, 1974; Laurent et al, 2010; Drasler et al, 2017)
A marked upregulation of cytochrome P450 enzyme and Kim-1 was observed in response to acetone and cisplatin, respectively, in kidney proximal tubule (PT) organoid (Astashkina et al, 2012)
Summary
Nanotechnology empowered by engineered nanomaterials has almost left no stone untouched in the scientific arena of the current century. The subtle but consistent early nanotoxicity signatures at metabolite, protein, or gene expression levels can be identified by using organoid models in conjunction with several cutting-edge analytical modalities Such as fluorescence-based methods, microfluidics, artificial intelligence, multi-omics integration, and single-cell analyses (Brazovskaja et al, 2019; Benning et al, 2020; Liu et al, 2020; Rodriguez-Garcia et al, 2020; Schuster et al, 2020; Tomasi et al, 2020; Costamagna et al, 2021; Duzagac et al, 2021). The utility of various organoid models to evaluate the toxicity of conventional as well as nano-drugs will be discussed under the current review along with associated challenges and future directions
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