Geometric and Electronic Structure‐Matched Superoxide Dismutase‐Like and Catalase‐Like Sequential Single‐Atom Nanozymes for Osteoarthritis Recession

Abstract

Abstract Highly‐active single‐atom nanoenzymes (SAzymes) with biomimetic geometric and electronic coordination structures are highly highlighted to exhibit greatly‐increased catalysis activity. Despite various SAzymes, superoxide dismutase (SOD)‐like SAzymes for scavenging superoxide anions to treat osteoarthritis are still absent. In this report, a graphene‐supported ClCuN 4 ‐centered SAzyme (CuN 4 ClG) is engineered that carries out SOD‐like reactions. Various synchrotron radiation‐based X‐ray valence/structural analyses reveal that the geometric and electronic structures of such ClCuN 4 active centers are validated to atomically match natural SOD enzyme after precisely manipulating coordinated N and Cl atoms via the unprecedented pre‐coordination orientation and preservation of copper‐phthalocyanine structure. Cu‐N 4 ClG SAzymes are endowed with unparalleled catalytic activities and kinetics to degrade O 2 • ¯ into H 2 O 2 and O 2 , and further exhibit catalase (CAT)‐like activity to sequentially decompose H 2 O 2 and • OH into H 2 O and O 2 , wherein the origin of sequential SOD‐like and CAT‐like catalysis routes is uncovered. Impressively, nitroxide radical scavenging and photothermally‐enhanced catalytic activity are reached, synergistically protecting chondrocytes from oxidative stress‐induced apoptosis and alleviating osteoarthritis via re‐programming or normalizing osteoarthritis microenvironments. Cu‐N 4 ClG SAzymes are competent for other reactive oxygen species (ROS)‐arised lesions, and their rationales provide guidance to design other SAzymes.