LAUSR

It is a big challenge to reveal the intrinsic cause of a nanotoxic effect due to diverse branches of signaling pathways induced by engineered nanomaterials (ENMs). Biotransformation of toxic ENMs involving biochemical reactions between nanoparticles (NPs) and biological systems has recently attracted substantial attention as it is regarded as the upstream signal in nanotoxicology pathways, the molecular initiating event (MIE). Considering that different exposure routes of ENMs may lead to different interfaces for the arising of biotransformation, this work summarizes the nano-bio interfaces and dose calculation in inhalation, dermal, ingestion, and injection exposures to humans. Then, five types of biotransformation are shown, including aggregation and agglomeration, corona formation, decomposition, recrystallization, and redox reactions. Besides, the characterization methods for investigation of biotransformation as well as the safe design of ENMs to improve the sustainable development of nanotechnology are also discussed. Finally, future perspectives on the implications of biotransformation in clinical translation of nanomedicine and commercialization of nanoproducts are provided.