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Repolarizing pro\u2010inflammatory M1 macrophages into the anti\u2010inflammatory M2 phenotype is emerging as a strategy to alleviate OA progression but is compromised by unsatisfactory efficiency. In this study, the reprogramming of mitochondrial dysfunction is pioneered with a camouflaged meta\u2010Defensome, which can transform M1 synovial macrophages into the M2 phenotype with a high efficiency of 82.3%. The meta\u2010Defensome recognizes activated macrophages via receptor\u2013ligand interactions and accumulates in the mitochondria through electrostatic attractions. These meta\u2010Defensomes are macrophage\u2010membrane\u2010coated polymeric nanoparticles decorated with dual ligands and co\u2010loaded with S\u2010methylisothiourea and MnO\n                    <jats:sub>2<\/jats:sub>\n                    . Meta\u2010Defensomes are demonstrated to successfully reprogram the mitochondrial metabolism of M1 macrophages by scavenging mitochondrial reactive oxygen species and inhibiting mitochondrial NO synthase, thereby increasing mitochondrial transcription factor A expression and restoring aerobic respiration. Furthermore, meta\u2010Defensomes are intravenously injected into collagenase\u2010induced osteoarthritis mice and effectively suppress synovial inflammation and progression of early OA, as evident from the Osteoarthritis Research Society International score. Therefore, reprogramming the mitochondrial metabolism can serve as a novel and practical approach to repolarize M1 synovial macrophages. The camouflaged meta\u2010Defensomes are a promising therapeutic agent for impeding OA progression in tclinic.\n                  <\/jats:p>","DOI":"10.1002\/adma.202202715","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T14:04:30Z","timestamp":1654610670000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":134,"title":["Reprogramming Mitochondrial Metabolism in Synovial Macrophages of Early Osteoarthritis by a Camouflaged Meta\u2010Defensome"],"prefix":"10.1002","volume":"34","author":[{"given":"Lei","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive Surgery Department of Orthopedic Surgery Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Branch of National Clinical Research Center for Orthopedics Sports Medicine and Rehabilitation  321 Zhongshan Road Nanjing Jiangsu 210008 P. 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