Current approaches for safer design of engineered nanomaterials.

The surge of applications for engineered nanomaterials (ENMs) across multiple industries raises safety concerns regarding human health and environmental impacts. ENMs can be hazardous through various mechanisms, including, particle dissolution and shedding of toxic metal ions, surface reactivity and perturbation of cellular membranes, lysosomal membrane damage, activation of inflammation pathways (e.g., NLRP3 inflammasome), etc. The aim of this review is therefore to discuss practical approaches for the safer design of ENMs through modification of their physicochemical properties that can lead to acute and/or chronic toxicity. This is premised on our understanding of how different ENMs induce toxicity within various biological systems. We will summarize studies that have investigated nanomaterial toxicity both in vitro and in vivo to understand the underlying mechanisms by which nanoparticles can cause inflammation, fibrosis, and cell death. With this knowledge, researchers have identified several design strategies to counter these mechanisms of toxicity. In particular, we will discuss how metal doping, surface coating and covalent functionalization, and adjustment of surface oxidation state and aspect ratio of ENMs could reduce their potential adverse effects. While these strategies might be effective under certain experimental and exposure scenarios, more research is required to fully apply this knowledge in real life applications of nanomaterials.