Cytotoxicity of C2N Originating from Oxidative Stress Instead of Membrane Stress

Two-dimensional (2D) nanomaterials have shown promising potential in a wide range of biomedical applications. Nevertheless, the rapid advances in this field recently have also evoked growing concerns about their toxic effects on humans and the environment. Herein, we systematically investigate the potential cytotoxicity of C2N nanosheets, a newly emerging 2D nitrogenized graphene with uniform holes in the basal plane. Our in vitro experiments show that C2N is toxic to human umbilical vein/vascular endothelium cells. The further combined experimental and theoretical studies unravel that the cytotoxicity of C2N mainly originates from its oxidative capability toward the antioxidant molecules, leading to excessive accumulation of reactive oxygen species in cells. Compared with graphene oxide, C2N exerts a relatively milder cytotoxicity, and importantly, this novel material shows negligible physical destruction effects on cell membranes, suggesting that C2N might be a potential alternative to graphene and its derivatives in biomedical research. This work sheds light on the cytotoxicity of C2N nanosheets and the underlying mechanism, which is crucial for the future utilization of this 2D nanomaterial in related biomedical fields.