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Presently, SA faces not only the deficient effectiveness of the gold\u2010standard systemic antibiotic therapy but also the scarcity of effective localized targeted approaches and standardized animal models. Herein, an ingenious multifunctional nanosystem is designed, which involves the methylation of hyaluronic acid (HA), copolymerization with DEGDA, loading with vancomycin (VAN), and then coating with fused macrophage\u2010platelet membrane (denoted as FM@HA@VAN). Upon intra\u2010articular administration, FM@HA@VAN nanoparticles exhibit sustained retention and selectively targeting to infected sites, leveraging macrophage\u2010mediated inflammation homing and platelet\u2010directed bacteria targeting. The acidic microenvironment triggers responsive release of vancomycin, leading to potent bactericidal effects. Subsequently, the exposed HA@VAN nanoparticles are efficiently internalized by activated macrophages, releasing HA to alleviate oxidative stress and achieve chondroprotection by inhibiting pro\u2010inflammatory cytokines, neutralizing ROS and upregulating macrophage M2 polarization. In vivo model and experiments confirm the efficacy of this dual\u2010targeting antibacterial approach, demonstrating its precision in eradicating bacterial infections and alleviating associated pathological processes, including synovial hyperplasia and cartilage erosion. The dual\u2010targeting therapeutic nanosystem, coordinated with fused\u2010membranes, holds promise for enhancing the treatment efficacy of SA.<\/jats:p>","DOI":"10.1002\/smll.202410710","type":"journal-article","created":{"date-parts":[[2025,1,19]],"date-time":"2025-01-19T22:48:49Z","timestamp":1737326929000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Fused Membrane\u2010Camouflaged Biomimetic Nanosystem for Dual\u2010Targeted Therapy of Septic Arthritis"],"prefix":"10.1002","volume":"21","author":[{"given":"Zeping","family":"Yu","sequence":"first","affiliation":[{"name":"Sports Medicine Center West China Hospital Sichuan University  Chengdu 610041 China"},{"name":"Department of Orthopedics and Orthopedic Research Institute West China Hospital Sichuan University  Chengdu 610041 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