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Current therapies lack lesion\u2010specificity and cause systemic side effects, highlighting the need for targeted treatment strategies. Here, we developed carrier\u2010free myricetin\u2010arginine conjugate nanozymes (MANZs) via a Mannich reaction\u2010mediated conjugation of\n                    <jats:sc>l<\/jats:sc>\n                    \u2010arginine and myricetin, followed by self\u2010assembly driven by noncovalent interaction. The MANZs selectively target M1 macrophages via cationic amino acid transporter 2 (CAT2)\u2010mediated uptake, facilitating preferential accumulation in inflamed joints. MANZs exert multi\u2010modal therapeutic effects by scavenging reactive oxygen species (ROS), repolarizing M1 macrophages, and inhibiting osteoclast differentiation. In a collagen\u2010induced arthritis (CIA) mouse model, MANZs significantly alleviated joint swelling, synovitis, and bone erosion without systemic toxicity. This work establishes a promising paradigm for RA therapy by integrating cationic amino acids with natural polyphenols into a self\u2010assembled, target\u2010specific nanoplatform with high biocompatibility and translational potential.\n                  <\/jats:p>","DOI":"10.1002\/advs.202521864","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T09:36:37Z","timestamp":1767605797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Self\u2010Assembled Myricetin\u2010Arginine Conjugate Nanozymes for Targeted Suppression of Joint Inflammation and Osteoclastogenesis in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9267-3340","authenticated-orcid":false,"given":"Jiachang","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, The Institute for Biomedical Engineering &amp; Nano Science, School of Medicine Tongji University  Shanghai P. 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