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Herein, an iron\u2010based SANzyme (Fe\u2010SANzyme) is rationally designed by edge\u2010site engineering, which intensively exposes edge\u2010hosted defective Fe\u2013N4<\/jats:sub> atomic sites anchored in hierarchical mesoporous structures. The Fe\u2010SANzyme exhibits excellent catalase\u2010like activity capable of efficiently catalyzing the decomposition of H2<\/jats:sub>O2<\/jats:sub> into O2<\/jats:sub> and H2<\/jats:sub>O, with a catalytic kinetic K<\/jats:italic>M<\/jats:sub> 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 H2<\/jats:sub>O2<\/jats:sub> and weaken the O\uf8ffO bond. By performing catalase\u2010like catalysis, the Fe\u2010SANzyme 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.<\/jats:p>","DOI":"10.1002\/adma.202205324","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T22:14:30Z","timestamp":1660256070000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":261,"title":["Edge\u2010Site Engineering of Defective Fe\u2013N4<\/sub> Nanozymes with Boosted Catalase\u2010Like Performance for Retinal Vasculopathies"],"prefix":"10.1002","volume":"34","author":[{"given":"Ruofei","family":"Zhang","sequence":"first","affiliation":[{"name":"CAS Engineering Laboratory for Nanozyme Key Laboratory of Protein and Peptide Pharmaceutical Institute of Biophysics Chinese Academy of Sciences Beijing 100101 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