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

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(center dot) over bar into H2O2 and O-2, and further exhibit catalase (CAT)-like activity to sequentially decompose H2O2 and (OH)-O-center dot into H2O 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.