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Iguratimod (IGU) is loaded, which inhibits inflammatory responses and osteoclast differentiation, into mesoporous polydopamine (MPDA), which scavenges ROS. Subsequently, the nanoparticles are coated with a cell membrane of macrophages to achieve actively targeted delivery of the nanoparticles to inflamed joints. It is shown that the M\u2010M@I nanoparticles are taken up well by lipopolysaccharide\u2010induced RAW 264.7 macrophages or bone marrow\u2010derived macrophages (BMDMs). In vitro, the M\u2010M@I nanoparticles effectively scavenge ROS, downregulate genes related to inflammation promotion and osteoclast differentiation, and reduce the proinflammatory cytokines and osteoclast\u2010related enzymes. They also reduce the polarization of macrophages to a pro\u2010inflammatory M1 phenotype and inhibit differentiation into osteoclasts. In mice with collagen\u2010induced arthritis, the M\u2010M@I nanoparticles accumulate at arthritic sites and circulate longer, significantly mitigating arthritis symptoms and bone destruction. These results suggest that the pathology\u2010specific biomimetic multifunctional nanoparticles are effective against rheumatoid arthritis, and they validate the approach of developing multifunctional therapies that target various pathological processes simultaneously.<\/jats:p>","DOI":"10.1002\/smll.202305197","type":"journal-article","created":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T02:58:44Z","timestamp":1698893924000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Ingenious Synergy of a Pathology\u2010Specific Biomimetic Multifunctional Nanoplatform for Targeted Therapy in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7905-0873","authenticated-orcid":false,"given":"Hong","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery and Orthopedic Research Institution West China Hospital Sichuan University  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