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Anti\u2010angiogenesis is emerging as a strategy for attenuating OA progression, but is often compromised by poor targeted drug delivery and immune clearance. Recent studies have identified macrophages formed a \u201cprotective barrier\u201d in the lining layer (LL) of synovium, which blocked the communication of joint cavity and sublining layer (SL) of synovium. Inspired by natural mimicry, macrophage membrane\u2010camouflaged drug delivery is explored to avoid immune clearance. Based on the single cell RNA sequencing, the CD34<jats:sup>+<\/jats:sup> synovial cells are identified as \u201csentinel cells\u201d for synovium angiogenesis. Consequently, CD34 antibody\u2010modified macrophage membrane\u00a0is constructed to target new angiogenesis. Hence, a biomimetic multi\u2010layered nanoparticle (NP) is developed that incorporates axitinib\u2010loaded poly(lactic\u2010co\u2010glycolic) acid (PLGA) with CD34 antibody modified macrophage membrane (Atb@NP@Raw@CD34) to specifically deliver axitinib (Atb) to the SL and sustain inhibiting angiogenesis without immune elimination. It is found that the Atb@NP@Raw@CD34 can pass through macrophage \u201cbarrier\u201d, specifically targeting CD34<jats:sup>+<\/jats:sup> cells, continuously releasing Atb and anti\u2010angiogenesis in OA synovitis. Furthermore, in vivo data demonstrated that Atb@NP@Raw@CD34 can attenuate joint degeneration by inhibiting synovium angiogenesis\u2010mediated synovitis. In conclusion, local injection of Atb@NP@Raw@CD34 presents a promising approach for clinically impeding OA progression.<\/jats:p>","DOI":"10.1002\/adhm.202401985","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:56:39Z","timestamp":1728953799000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Macrophage Membrane\u2010Biomimetic Multi\u2010Layered Nanoparticles Targeting Synovial Angiogenesis for Osteoarthritis Therapy"],"prefix":"10.1002","volume":"14","author":[{"given":"Junyi","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery The First Affiliated Hospital of Chongqing Medical University  Chongqing 400016 China"},{"name":"Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine Orthopaedic Research Laboratory of Chongqing Medical University  Chongqing 400016 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