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

Abstract Acute liver injury, a critical public health issue with rapid hepatocellular dysfunction, is linked to ROS-mediated oxidative stress and inflammation. Nanozymes show therapeutic 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 excellent fluorescence (QY > 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 against acetaminophen-induced injury by efficiently scavenging ROS, 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 improvement of hepatic function, preservation of mitochondrial integrity, and reduction of proinflammatory cytokine levels. With excellent biocompatibility, favorable hepatic tropism, and coordinated regulation of oxidative and apoptotic pathways, MgMn@CDs represent a promising nanozyme platform for mitigating acute liver injury.