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Unfortunately, current treatment regimens fail to cure RA due to low therapeutic responses and off\u2010target side effects. Herein, a neutrophil membrane\u2010cloaked, natural anti\u2010arthritic agent leonurine (Leo), and catalase (CAT) co\u2010loaded nanoliposomal system (Leo@CAT@NM\u2010Lipo) is constructed to remodel the hostile microenvironment for RA remission. Due to the inflammation tropism inherited from neutrophils, Leo@CAT@NM\u2010Lipo can target and accumulate in the inflamed joint cavity where high\u2010level ROS can be catalyzed into oxygen by CAT to simultaneously accelerate the drug release and alleviate hypoxia at the lesion site. Besides, the neutrophil membrane camouflaging also enhances the anti\u2010inflammatory potentials of Leo@CAT@NM\u2010Lipo by robustly absorbing pro\u2010arthritogenic cytokines and chemokines. Consequently, Leo@CAT@NM\u2010Lipo successfully alleviated paw swelling, reduced arthritis score, mitigated bone and cartilage damage, and reversed multiple organ dysfunctions in adjuvant\u2010induced arthritis rats (AIA) rats by synergistic effects of macrophage polarization, inflammation resolution, ROS scavenging, and hypoxia relief. Furthermore, Leo@CAT@NM\u2010Lipo manifested excellent biocompatibility both at the cellular and animal levels. Taken together, the study provided a neutrophil\u2010mimetic and ROS responsive nanoplatform for targeted RA therapy and represented a promising paradigm for the treatment of a variety of inflammation\u2010dominated diseases.<\/jats:p>","DOI":"10.1002\/smll.202307379","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T16:53:20Z","timestamp":1702400000000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Neutrophil\u2010Mimetic, ROS Responsive, and Oxygen Generating Nanovesicles for Targeted Interventions of Refractory Rheumatoid Arthritis"],"prefix":"10.1002","volume":"20","author":[{"given":"Zhuang","family":"Tang","sequence":"first","affiliation":[{"name":"School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macao 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Meng","sequence":"additional","affiliation":[{"name":"School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macao 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxue","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macao 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macao 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macao 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macao 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefan","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macao 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xican","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macao 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering and Technology Sun Yat\u2010sen University  Zhuhai 519082 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Zhun","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macao 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2870-1111","authenticated-orcid":false,"given":"Xiaolin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macao 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,12]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30173-8"},{"key":"e_1_2_8_2_1","first-page":"591","volume":"18","author":"Finckh A.","year":"2022","journal-title":"Nat. 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