Yingcan Zhao, Dan Wu
) have shown great potential in various applications due to their unique physicochemical properties. Several in vitro studies have indicated that MXene nanosheets may exhibit toxic effects. However, the underlying mechanisms responsible for its potential toxicity remain poorly understood. In this study, we demonstrate that MXene nanosheets exhibit intrinsic DNA cleavage activity toward the supercoiled plasmid pBR322 under dark conditions without requiring external energy input. The cleavage efficiency was concentration-, time-, temperature-, and pH-dependent, with higher pH promoting reactive oxygen species (ROS) generation via superoxide anion formation. Furthermore, MXene nanosheets acted as catalytic intermediates facilitating electron transfer from β-nicotinamide adenine dinucleotide (NADH) to molecular oxygen, significantly enhancing DNA cleavage in the presence of NADH. Systematic investigations revealed that the cleavage efficiency increased with prolonged incubation time and higher concentrations of both MXene and NADH. This study highlights the potential environmental risks of MXene nanomaterials in aquatic systems due to their ROS-generating and DNA-cleaving capabilities, while also suggesting their promising applications in DNA manipulation and environmental biotechnology.