Mg/Mn bi-single-atom carbon dot nanozymes with enhanced SOD-like activity and fluorescence for hepatoprotection

Acute liver injury, a critical clinical and public health challenge characterized by rapid hepatocellular dysfunction, is closely associated with ROS-mediated oxidative stress and inflammation. Nanozymes show protective promise via ROS scavenging but suffer from low catalytic efficiency and insufficient self-tracing capacity. Herein, we report Mg, Mn co-doped CD (MgMn@CD) nanozymes with ultra-high SOD-like activity (> 20000 U/mg) and satisfactory fluorescence (quantum yield > 16%). Both Mg and Mn are distributed in the CD structure in a single-atom state. Mg doping promotes the conversion of ketone to enol structures in the CD structure, thereby increasing the structural rigidity and improving fluorescence quantum yield. Meanwhile, Mn synergistically enhances SOD-like activity through coordination with ketone structures and nitrogen-containing structures in the CD structure. MgMn@CD nanozymes demonstrate strong hepatoprotective effects against acetaminophen-induced injury by efficiently scavenging reactive oxygen species, restoring mitochondrial function, and suppressing apoptosis, ferroptosis, and inflammation. In vitro studies confirm their antioxidant and cytoprotective effects, while in vivo experiments show dose-dependent improvements in hepatic function, preservation of mitochondrial integrity, and reduction of proinflammatory cytokine levels. With excellent biocompatibility, favorable hepatic tropism, and coordinated regulation of oxidative stress and apoptotic signaling pathways, MgMn@CDs represent a promising nanozyme platform for mitigating acute liver injury.