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Disease\u2010modifying treatments for OA are currently lacking. Because inflammation mediated by an imbalance of M1\/M2 macrophages in the synovial cavities contributes to OA progression, regulating the M1 to M2 polarization of macrophages can be a potential therapeutic strategy. Basing on the inherent immune mechanism and pathological environment of OA, an immunoglobulin G\u2010conjugated bilirubin\/JPH203 self\u2010assembled nanoparticle (IgG\/BRJ) is developed, and its therapeutic potential for OA is evaluated. After intra\u2010articular administration, IgG conjugation facilitates the recognition and engulfment of nanoparticles by the M1 macrophages. The internalized nanoparticles disassemble in response to the increased oxidative stress, and the released bilirubin (BR) and JPH203 scavenge reactive oxygen species (ROS), inhibit the nuclear factor kappa\u2010B pathway, and suppress the activated mammalian target of rapamycin pathway, result in the repolarization of macrophages and enhance M2\/M1 ratios. Suppression of the inflammatory environment by IgG\/BRJ promotes cartilage protection and repair in an OA rat model, thereby improving therapeutic outcomes. This strategy of opsonization involving M1 macrophages to engulf carrier\u2010free BR\/JPH203 nanoparticles to suppress inflammation for OA therapy holds great potential for OA intervention and treatment.<\/jats:p>","DOI":"10.1002\/advs.202400713","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T16:09:18Z","timestamp":1712678958000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Opsonization Inveigles Macrophages Engulfing Carrier\u2010Free Bilirubin\/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2058-4723","authenticated-orcid":false,"given":"Huirong","family":"Huang","sequence":"first","affiliation":[{"name":"Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou 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