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The activated macrophages\u2010mediated inflammation\u2010oxidative stress storm seriously hindered diabetic wound healing. However, currently available anti\u2010inflammatory and antioxidative drugs have limited efficacy due to non\u2010continuous activity and poor accumulation within activated macrophages. Herein, a novel Cu\u2010based metal\u2010organic framework (Cu\u2010MOF) was coated with dextran sulfate (DSS) to develop an activated macrophage\u2010targeted CuMD nanozyme. Such CuMD nanozymes exhibit excellent activated macrophage targeting ability via the specific binding between DSS and macrophage scavenger receptor A. And CuMD nanozyme can also effectively scavenge excessive reactive oxygen species via stable multiple antioxidant enzyme activities, inhibit inflammatory cytokine secretion, and promote macrophage polarization towards M2 phenotype through MYD88\/TAB\/NF\u2010kappa B Signaling Pathway. Furthermore, CuMD\u2010loaded microneedle patches (CuMD\u2010MN) can penetrate the skin surface barrier and slowly release CuMD. In a diabetic mouse skin defect model, CuMD\u2010MN remarkably suppressed inflammation\u2010oxidative stress storm, resulting accelerated tissue regeneration wound healing. These findings highlight the potential of CuMD\u2010MN a promising treatment modality for diabetic wound.<\/jats:p>","DOI":"10.1002\/smll.75570","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:58:32Z","timestamp":1789196312000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophage\u2010Targeted Nanozyme Interrupts Inflammation\u2010Oxidative Stress Storm in Diabetic Wound Healing"],"prefix":"10.1002","volume":"22","author":[{"given":"Bin","family":"Cheng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases and National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Chengdu Sichuan 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