Cellular uptake and cytotoxicity of PEGylated MXene nanomaterials mediated by protein corona

A stringent analysis of the biocompatibility of MXene is a necessary condition for assessing the biological risk of MXene. Owing to high surface free energy, MXene is capable of adsorbing a large amount of blood proteins to form MXene-protein corona complexes, however, a comprehensive understanding of the relationship between MXene and cellular physiological systems remains limited. Therefore, we investigated the cellular uptake and cytotoxicity effect of MXene Ti3C2Tx and PEGylation Ti3C2Tx mediated by human serum protein corona in THP-1 cells. It was found that PEGylation can alter the interaction between Ti3C2Tx and serum proteins, inducing a significant transformation in the fingerprint of the protein corona. Following protein corona formation, both Ti3C2Tx and PEGylated Ti3C2Tx predominantly accumulated at lysosomal sites within THP-1 cells. Further analysis revealed that clathrin-mediated endocytosis was the primary mechanism of Ti3C2Tx internalization by THP-1 cells. There was no significant effect on cell viability. However, we found that Ti3C2Tx plays a dual role as both a stimulus and scavenger of ROS within THP-1 cells, influenced by its PEGylation and the formation of a protein corona. This study provides important insights for biocompatibility evaluation and rational design of nanoproducts based on Ti3C2Tx in the future.