Enzyme-Mimicking Atomic Zn−P Catalytic Pairs for Anti-inflammatory Therapy

Natural enzymes are widely used in theranostics, but they suffer from poor stability, high costs, and nontunable monofunctionality, driving the development of artificial enzymes, in particular single-atom nanozymes (SAzymes). However, conventional SAzymes struggle to handle multistep redox reactions effectively. Herein, we present atomically dispersed zinc−phosphorus (Zn−P) catalytic pairs (CPs) anchored on acid-resistant carbon nanosheets (Zn−P/CNS) that display greatly enhanced multienzyme-like activities, particularly for superoxide radical dismutation and hydrogen peroxide decomposition. Density functional theory reveals that P primarily serves as an additional catalytic site to facilitate substrate binding and intermediate stabilization, while also modulating the local electronic structure of Zn and aiding proton transfer, thereby lowering energy barriers in the multistep redox pathways. In a dextran sulfate sodium-induced colitis model, oral administration of this Zn−P/CNS markedly reduces oxidative damage and inflammation, demonstrating the promise of metal−nonmetal CPs as a versatile platform for designing high-performance nanozymes for biomedical applications.