Biotransformation of graphene oxide nanosheets in blood plasma affects their interactions with cells

Blood is the main biological fluid of humans and most animals. Understanding the effects of the biotransformation of nanomaterials in blood plasma on their interactions with cells is fundamental for the evaluation of their health risks and applications. However, there is a lack of related information. The present work found that free radicals and biological molecules in human blood plasma simultaneously drive the formation of a biological corona on biodegraded graphene oxide (GO) nanosheets. Importantly, the above biotransformation affected the interactions of GO with cells. For example, the biotransformed GO induced lower levels of reactive oxygen species and cell ultrastructure damage than did the pristine GO. In addition to the well-known protein corona, the small-molecule corona on the biodegraded GO also plays a critical role in the reduction of GO cytotoxicity through quenching excessive free radical generation. Metabolomic analysis revealed that the biotransformation reduced the oxidative stress induced by GO mainly via upregulation of the fatty acid metabolism and downregulation of the galactose metabolism. Overall, the present work clearly shows that the biotransformation of GO in blood plasma influences the nanotoxicity of GO. Compared with pristine nanomaterials, biotransformed materials are more biologically relevant to assessments of their environmental health risks.