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Regrettably, RA remains incurable owing to insufficient therapeutic response along with severe side reactions of available treatments. To overcome these formidable obstacles, an M2 macrophage membrane\u2010cloaked, ROS\u2010sensitive lipid\u2010gated, and herbal anti\u2010arthritic agent celastrol (Cel)\u2010loaded hybrid silica nanosystem (Cel@M2\u2010L\u2010MSN) was established to reshape the intricate RA microenvironment. Benefiting from cell membrane camouflaging, Cel@M2\u2010L\u2010MSN inherited the inflammation\u2010homing capability of M2 macrophages and selectively accumulated in the inflamed joints, where excessive ROS triggered Cel release from the mesopores to exert anti\u2010inflammatory and antioxidative effects for joint protection. Moreover, Cel@M2\u2010L\u2010MSN demonstrated strengthened anti\u2010inflammatory capability by robustly sponging multiple pro\u2010arthritogenic factors including TNF\u2010\u03b1, IL\u20101\u03b2, and CCL\u20102. In adjuvant\u2010induced arthritis (AIA) rats, Cel@M2\u2010L\u2010MSN tremendously alleviated arthritis symptoms, mitigated cartilage and bone degeneration, and attenuated major organ injuries by playing multiple roles including inflammation downregulation, ROS clearance, and macrophage repolarization. Furthermore, Cel@M2\u2010L\u2010MSN substantially enhanced the cyto\/hemocompatibility of free Cel and manifested good biosafety in vivo. Collectively, this study presents a biohybrid and stimuli\u2010responsive nanomedicine for targeted RA remission, which also holds great promise for the clinical intervention of a wide spectrum of refractory inflammatory diseases.<\/jats:p>","DOI":"10.1002\/exp.20230030","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:56:13Z","timestamp":1787201773000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["M2 Macrophage\u2010Mimetic and ROS\u2010Sensitive Hybrid Nanoplatform for Targeted Alleviation of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"6","author":[{"given":"Yi","family":"Xiao","sequence":"first","affiliation":[{"name":"School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macao 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