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Activated fibroblast\u2010like synoviocytes (FLSs), abundant in RA synovium, crucially facilitate disease progression. These activated FLSs drive RA pathogenesis by upregulating adhesion molecules, proinflammatory cytokines, chemokines, and major histocompatibility complex class II (MHC\u2010II). This upregulation facilitates their interaction with CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, triggering an inflammatory cascade that exacerbates synovial inflammation. To address this, a DSPE\u2010mPEG\n                    <jats:sub>2000<\/jats:sub>\n                    \u2010GPA\u2010KLVFF\u2010decorated liposome loaded with dexamethasone (DPGK@Lipo\u2010Dex) is developed to precisely target FLSs in arthritic joints. DPGK@Lipo\u2010Dex achieves efficient binding to FLSs through a specific enzymatic interaction between fibroblast activation protein\u2010\u03b1 (FAP\u2010\u03b1) and GPA, along with prolonged retention in the joints due to the fibrillar transformation of KLVFF. In vitro studies demonstrate that DPGK@Lipo\u2010Dex enhances cellular uptake and reduces MHC\u2010II expression on aggressive FLSs. In adjuvant\u2010induced arthritis (AIA) rats, DPGK@Lipo shows specific distribution patterns that target both inflamed joints and FLSs. Treatment with DPGK@Lipo\u2010Dex leads to a downregulation of MHC\u2010II expression, a decrease in the number of activated T cells within the synovium, and a reduction in levels of proinflammatory mediators. Overall, DPGK@Lipo\u2010Dex effectively suppresses FLSs\u2010related responses and ultimately results in inflammatory remission. This makes DPGK@Lipo\u2010Dex a promising candidate for nano\u2010therapeutic treatment in rheumatoid arthritis.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202503277","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T06:05:41Z","timestamp":1757570741000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Transformable Nanoplatform Precisely Positions Fibroblast\u2010Like Synoviocytes via FAP\u2010\u03b1 for Improved Rheumatoid Arthritis Therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Chenglong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacy Sichuan Clinical Medical Research Center for Neurological Diseases Deyang Key Laboratory of Tumor Molecular Research Deyang People's Hospital Affiliated Hospital of Chengdu University of Traditional Chinese Medicine  Deyang 618000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Stomatology Deyang People's Hospital Affiliated Hospital of Chengdu University of Traditional Chinese Medicine  Deyang 618000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sichuan Clinical Medical Research Center for Neurological Diseases Deyang Key Laboratory of Tumor Molecular Research Deyang People's Hospital Affiliated Hospital of Chengdu University of Traditional Chinese Medicine  Deyang 618000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaiyu","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Sichuan Clinical Medical Research Center for Neurological Diseases Deyang Key Laboratory of Tumor Molecular Research Deyang People's Hospital Affiliated Hospital of Chengdu University of Traditional Chinese Medicine  Deyang 618000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Deyang People's Hospital Affiliated Hospital of Chengdu University of Traditional Chinese Medicine  Deyang 618000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Personalized Drug Research and Therapy Key Laboratory of Sichuan Province Sichuan Provincial People\u2019s Hospital School of Medicine University of Electronic Science and Technology of China Chengdu 610072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0380-3517","authenticated-orcid":false,"given":"Sanjun","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources, College of Modern Chinese Medicine Industry School of Pharmacy Chengdu University of Traditional Chinese Medicine Chengdu 611137 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.0786"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-018-0016-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntm.2024.100051"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31491-5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2020.1777279"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/RHU.0000000000000490"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt.13.94"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jobcr.2021.02.009"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202306143"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202207490"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1263-7"},{"key":"e_1_2_9_10_2","first-page":"137","volume":"4","author":"Luo H.","year":"2025","journal-title":"Acta Mater. 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