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While cobalt\u2010based metal\u2010organic framework (MOF) nanozymes are potent catalase (CAT) mimics, their therapeutic efficacy is crippled by an inherently weak superoxide dismutase (SOD)\u2010like activity that prevents full\u2010chain ROS scavenging. Here, we resolve this imbalance through an innovative \u201cpre\u2010embedding\/activation\u201d strategy. This approach involves pre\u2010embedding Zn\n                    <jats:sup>2+<\/jats:sup>\n                    into a cobalt\u2010based framework to create a stable yet activatable precursor. The subsequent dopamine (DA)\u2010driven \u201cactivation\u201d then remodels the latent Zn\/Co\u2010N coordination sites, unlocking an efficient SOD\u2010to\u2010CAT catalytic relay by synergistically amplifying the SOD\u2010like activity for seamless elimination of the entire ROS cascade. This powerful scavenging capability restores mitochondrial function and reprograms macrophages toward an anti\u2010inflammatory M2 phenotype by inhibiting the ROS\u2010mediated S100A8\/NF\u2010\u03baB signaling axis and its destructive positive feedback loop. The resulting immunomodulation translates to profound therapeutic outcomes in a rat OA model, where it simultaneously promotes chondrocyte anabolism to achieve significant cartilage repair while suppressing peripheral nerve sensitization to provide sustained pain relief. Our work thus establishes nanoscale interfacial reconstruction as a powerful and rational platform for engineering sophisticated catalytic relays within nanozymes for advanced biomedical applications.\n                  <\/jats:p>","DOI":"10.1002\/adma.72747","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T11:37:42Z","timestamp":1773142662000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Unlocking an Efficient SOD\u2010to\u2010CAT Catalytic Relay in a MOF Nanozyme via Dopamine\u2010Driven Interfacial Nanoreconstruction for Osteoarthritis Therapy"],"prefix":"10.1002","volume":"38","author":[{"given":"Zhiqiang","family":"Li","sequence":"first","affiliation":[{"name":"Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang 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