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Inadequate perfusion resulting from capillary rarefaction can, in turn, induce chronic tissue hypoxia and exacerbate ischemic acute tubular necrosis, leading to an \u201coxidative stress\u2010microvascular perfusion\u201d negative feedback that further aggravate kidney damage. In this study, a macrophage membrane\u2010camouflaged manganese\u2010based antioxidant nanozyme (MB@LM) is developed for targeted delivery and oxidative stress relief in AKI therapy. By inheriting macrophage surface proteins, MB@LM selectively targets damaged renal tissues that overexpress adhesion molecules like intercellular adhesion molecule\u20101 (ICAM\u20101) and vascular cell adhesion molecule\u20101 (VCAM\u20101), facilitating enhanced accumulation at the injury site. The manganese\u2010based nanozyme core provides antioxidant enzyme\u2010mimicking activities, effectively reducing oxidative stress and inhibiting apoptosis. In IRI\u2010induced AKI mouse model, MB@LM treatment significantly reduces renal damage, restores renal microvascular perfusion as assessed by ultrasound imaging, and alleviated inflammation, demonstrating remarkable therapeutic efficacy. Overall, MB@LM represents a promising targeted therapy for AKI, offering precise delivery, potent antioxidant protection, and anti\u2010inflammatory effects to support renal recovery and improve outcomes for AKI.<\/jats:p>","DOI":"10.1002\/adhm.202405090","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T03:00:26Z","timestamp":1738724426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Macrophage Membrane\u2010Camouflaged Nanozymes for Combating the Oxidative Stress\u2010Microvascular Perfusion Negative Feedback in Ischemia\u2010Reperfusion Induced Acute Kidney Injury"],"prefix":"10.1002","volume":"14","author":[{"given":"Fan","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Ultrasound in Medicine Sir Run Run Shaw Hospital School of Medicine Zhejiang University  Hangzhou 310016 China"},{"name":"Department of Pharmacy Sir Run Run Shaw Hospital School of 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