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Herein, we propose a novel spatiotemporal ultrasound-responsive microcapsule carrier to reinforce curcumin-based sonodynamic therapy in treating RA. Based on microfluidic technology, microcapsules with a hydrogel shell loaded with curcumin and a perfluorocarbon core enriched with oxygen (CUR\/O\n                    <jats:sub>2<\/jats:sub>\n                    -MCs) can be obtained. Ascribed to the liquid-to-gas transition property of perfluorocarbon and the sonosensitivity of curcumin, ultrasound stimulation can realize controlled oxygen release followed by sonodynamic reactive oxygen species production. We have demonstrated that the ultrasound-activated CUR\/O\n                    <jats:sub>2<\/jats:sub>\n                    -MCs can elevate reactive oxygen species amounts in overproliferating fibroblast-like synoviocytes, subsequently inducing fibroblast-like synoviocyte apoptosis. In addition, the released curcumin and oxygen can bring about macrophage repolarization, antiangiogenesis, and hypoxia alleviation, which are also important in blocking RA progression. Thus, in collagen-induced arthritis rats, our spatiotemporal sonodynamic microcapsules can attenuate symptoms and reduce joint damage. These results indicate that our ultrasound-responsive multifunctional microcapsule is an ideal candidate for sonodynamic therapy enhancement and RA treatment.\n                  <\/jats:p>","DOI":"10.34133\/research.0844","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T03:17:34Z","timestamp":1753759054000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":6,"title":["Multi-component Microcapsules Derived Spatiotemporal Sonodynamic Reinforcing Therapy against Rheumatoid Arthritis"],"prefix":"10.34133","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3495-231X","authenticated-orcid":true,"given":"Danqing","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Institute of Translational Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, \rNanjing University, Nanjing 210002, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Institute of Translational Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, \rNanjing University, Nanjing 210002, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Institute of Translational Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, \rNanjing University, Nanjing 210002, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, \rNanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Institute of Translational Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, \rNanjing University, Nanjing 210002, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7875-0018","authenticated-orcid":true,"given":"Yuanjin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Institute of Translational Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, \rNanjing University, Nanjing 210002, China."},{"name":"Department of Rheumatology and Immunology, \rNanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, China."},{"name":"Institute of Organoids on Chips Translational Research, \rHenan Academy of Sciences, Zhengzhou 450009, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Institute of Translational Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, \rNanjing University, Nanjing 210002, China."},{"name":"Department of Rheumatology and Immunology, \rNanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"issue":"9746","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/S0140-6736(10)60826-4","article-title":"Rheumatoid arthritis","volume":"376","author":"Scott DL","year":"2010","unstructured":"Scott DL, Wolfe F, Huizinga TW. 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