Edge‐Site Engineering of Defective Fe–N4 Nanozymes with Boosted Catalase‐Like Performance for Retinal Vasculopathies

Abstract Extensive efforts are devoted to refining metal sites for optimizing the catalytic performance of single‐atom nanozymes (SANzymes), while the contribution of the defect environment of neighboring metal sites lacks attention. Herein, an iron‐based SANzyme (Fe‐SANzyme) is rationally designed by edge‐site engineering, which intensively exposes edge‐hosted defective Fe–N 4 atomic sites anchored in hierarchical mesoporous structures. The Fe‐SANzyme exhibits excellent catalase‐like activity capable of efficiently catalyzing the decomposition of H 2 O 2 into O 2 and H 2 O, with a catalytic kinetic K M value superior to that of natural catalase and reported nanozymes. The mechanistic studies depict that the defects introduce notable charge transfer from the Fe atom to the carbon matrix, making the central Fe more activated to strengthen the interaction with H 2 O 2 and weaken the OO bond. By performing catalase‐like catalysis, the Fe‐SANzyme significantly scavenges reactive oxygen species (ROS) and alleviates oxidative stress, thus eliminating the pathological angiogenesis in animal models of retinal vasculopathies without affecting the repair of normal vessels. This work provides a new way to refine SANzymes by engineering the defect environment and geometric structure around metal sites, and demonstrates the potential therapeutic effects of the nanozyme on retinal vasculopathies.