Rational Design of Carbon Dot‐Supported Mn─Zn Bimetallic Single‐Atom Nanozymes for Enhancing SOD‐Like Activity and Fluorescence

ABSTRACT Nanozymes provide a novel therapeutic strategy for reactive oxygen species‐related diseases, yet they still suffer from low catalytic efficiency and the lack of analytical tools for in vivo processes. Herein, by integrating Zn and Mn into CDs through coordination, red emissive CD nanozymes (ZnMnCDs) with ultrahigh superoxide dismutase (SOD)‐like activity (>20 000 U/mg) and excellent fluorescence (quantum yield > 7%) are rationally designed. Mn 2+/3+ coordinates with furan and amide groups in the CDs to form a MnN 2 O 2 /MnN 3 O 1 configuration, reducing the adsorption of · OH, and finally improving SOD‐like activity of CDs. Zn 2+ coordinating with N/O‐containing functional groups of the CDs blocks excited‐state intramolecular proton transfer and increases the structural rigidity of the CDs, leading to a 34‐fold increase in the fluorescence intensity of the CDs with the same Mn doping content. In a male C57BL/6 mouse model of renal ischemia‐reperfusion, ZnMnCDs exhibit significant accumulation in the kidney and show a prominent therapeutic effect on acute kidney injury. Furthermore, the red fluorescence and high quantum yield of ZnMnCDs enable their self‐tracking capacity in vivo. This work provides important insights and guidance for the design of nanozymes with high catalytic activity and good fluorescence, and offers a new therapeutic strategy for ROS‐related diseases.