Effects of microenvironmental factors on assessing nanoparticle toxicity

Abstract

Nanoparticles, such as dust or fine particles produced from diverse sources, are regarded as hazardous materials to human organs, and the interest in understanding their biological mechanisms and evaluating the cellular response of nanoparticles is growing. The toxicity of nanoparticles is determined by several factors associated with not only their own properties, but also the surrounding microenvironmental factors of the cell. However, owing to its simplicity, in vitro-based evaluation of nanomaterial toxicity has been conventionally performed using a monolayer cell sheet cultured on a stiff surface in a static environment. Although 2D-based static models efficiently provide rapid assay results, the cytotoxicity of nanomaterials is frequently over- or underestimated due to the low consideration of the microenvironmental factors observed in vivo. To overcome the issue of low predictivity of conventional toxicity assays, many researchers have replicated some physiological factors when monitoring cellular responses induced by nanoparticles. In this review, we classify these microenvironmental factors and summarise their effects on cellular cytotoxicity evaluated in in vitro models that recapitulate the physiological microenvironment. Cellular toxicity upon exposure to nanoparticles was found to be different in the presence of physiological conditions, including vascular geometries, fluidic conditions, cyclic stretching, physical barriers, and cell-cell interactions; in some cases, these results are more like those observed in vivo. Our results imply that the consideration of microenvironmental factors is indispensable to provide more useful and reliable information than that provided by conventional 2D-based static in vitro testing platforms.