Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation

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.

Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment

“…So, worldwide research groups are dedicating efforts to develop a new generation of advanced in vitro models capable of recapitulating organ functions becoming effective tools for toxicology, pharmacology (investigating drug metabolism, pharmacokinetics, and toxicity), and for the mechanistic understanding of organ physiology and pathophysiology [ 150 , 153 , 154 , 155 ]. Several promising advanced models have been already established with superior physiological relevance, correlation, and validation compared to in vivo models [ 149 , 150 , 151 , 153 , 154 , 156 , 157 , 158 ]. However, it is important to stress that the priority in model development was not for nanosafety purposes.…”

“…These seem to be suited to the assessment of skin-related nanomaterial risk [ 159 ]. Three-dimensional skin models exposed to nanomaterials provided more realistic analyses with lesser nanomaterial penetration due to an enhanced barrier function [ 158 , 159 ]. Oral epithelium and urogenital tract tissues are already commercially available; however, few companies provide relevant essential organs for nanomaterial safety such as the liver, kidney, respiratory epithelium, and intestinal epithelium [ 149 , 150 , 151 , 152 , 153 , 160 ].…”

“…Liver, kidney, brain, skin, lung, and intestinal organoids among others were already established, and they are also considered promising tools for predicting nanomaterial toxicity to organs [ 150 ]. They provide organotypic cytoarchitectures with a spatially organized structure and in vivo phenotypic and extracellular matrix (ECM) expression mimicking important cellular functions such as cell migration, differentiation, and apoptosis, among other advantages [ 158 ]. In nanotoxicological studies, organoids seem to offer a barrier to nanomaterial distribution and cytotoxicity [ 9 , 152 ].…”

“…Alternatively, 3D biomaterial-based models also present multiple benefits, since they are constituted by synthetic or naturally derived biomaterials, mimicking cell–ECM interactions [ 156 , 163 , 164 ]. With the latest improvements in materials science, microfabrication techniques, and bioreactor-based spheroid and organoid technology [ 153 ], new efforts are being made to combine self-organizing 3D biological structures into organs-on-chips (OoCs) to emulate both the structural and dynamic complexity of tissues and organs [ 153 , 158 , 165 , 166 , 167 ].…”

“…Integrated multiorganoid models have been proposed in an effort to mimic complex procedures of metabolism and responses at the multiorganoid level, where flow rates resemble blood circulation in the human body [ 176 ]. Therefore, MOoCs can be exploited to evaluate the systemic toxicity of nanomaterials from the dynamic process of distribution, absorption, metabolism, and excretion features; nonetheless, systemic predictions are still challenging [ 157 , 158 ]. Future studies should take advantage of the development of engineered perfusable vasculature in microphysiological platforms making it possible to mimic the delivery of nanomaterials in a more physiologically relevant way, allowing the accurate prediction of their performance in vivo [ 153 , 166 ].…”