Evaluating the Cytotoxicity of Ti₃C₂ MXene to Neural Stem Cells

MXenes have attracted extensive attention due to their unique physicochemical properties. Especially, the flexibility and good conductivity endow MXenes with a great application prospect in the neural interfaces. However, the cytotoxicity of MXenes to nervous system remains unclear. In this study, we evaluated the cytotoxicity of Ti₃C₂ (the most studied MXenes) using primary neural stem cells (NSCs) and NSCs-derived differentiated cells in terms of apoptosis, viability, cellular uptake, cell membrane integrity, and global gene expression profiles. We found that 12.5 μg/mL Ti₃C₂ had no observable adverse effect on NSCs and NSCs-derived differentiated cells. However, 25 μg/mL Ti₃C₂ induced significant cytotoxicity and were internalized into the NSCs cells with compromised cell membrane. Furthermore, in the NSCs exposure to 25 μg/mL Ti₃C₂, we identified 198 differently expressed genes (DEGs), which were mainly associated with the extracellular region. Besides, the DEGs were involved in inflammatory, defense, stress, and stimulus response. This work will improve our understanding of biocompatibility of MXenes in the nervous system and promote the biomedical application of MXenes.