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However, current therapies have limitations in ocular targeting, in controlling reactive oxygen species (ROS), and in regulating key inflammatory pathways. In this study, we develop a mannosylated biomimetic nanocloak (H-151-Cu\/Zn-MOF@LM@Man) that combines active targeting, ROS scavenging, and STING pathway inhibition for a synergistic approach to treating autoimmune uveitis. This nanoplatform consists of a copper\u2013zinc bimetallic metal\u2013organic framework (Cu\/Zn-MOF) loaded with the STING antagonist H-151 and coated with a hybrid membrane made from macrophage-derived membranes and mannosylated liposomes (LM@Man). After systemic injection, the nanocloak passively homes to inflamed tissues through membrane camouflage and actively targets mannose receptor\u2013expressing immune cells. It efficiently crosses the blood\u2013retinal barrier (BRB) and accumulates at intraocular lesions. At the inflammation site, the Cu\/Zn-MOF core scavenges excess ROS using nanozyme activity. At the same time, H-151 inhibits the STING\u2013TBK1\u2013NF-\u03baB pathway, reshaping macrophage and microglia phenotypes, and restoring immune balance. This closed-loop system effectively reduces inflammatory cytokine production, lessens tissue damage, and enhances therapeutic precision. Overall, this study presents a multifunctional, translatable nanoplatform that enables targeted delivery, redox control, and immune reprogramming\u2500offering a promising strategy for treating autoimmune uveitis and other inflammation-related disorders.<\/jats:p>","DOI":"10.1021\/acsnano.6c06477","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T07:02:17Z","timestamp":1786086137000},"page":"22696-22715","source":"Crossref","is-referenced-by-count":0,"title":["Synchronous Reactive\nOxygen Species Scavenging and\nImmunomodulation for Autoimmune Uveitis Therapy by a Mannosylated\nBiomimetic Nanocloak"],"prefix":"10.1021","volume":"20","author":[{"given":"Jia","family":"Shu","sequence":"first","affiliation":[{"name":"Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doudou","family":"Ling","sequence":"additional","affiliation":[{"name":"Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3904-7397","authenticated-orcid":true,"given":"Siqiao","family":"Li","sequence":"additional","affiliation":[{"name":"Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiping","family":"Wu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Chongqing Medical University, Jinfeng Laboratory , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinjin","family":"Dai","sequence":"additional","affiliation":[{"name":"Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Huang","sequence":"additional","affiliation":[{"name":"Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[{"name":"Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfeng","family":"Cao","sequence":"additional","affiliation":[{"name":"Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guannan","family":"Su","sequence":"additional","affiliation":[{"name":"Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]},{"name":"Fudan University , , ,","place":["Shanghai, China, 200030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2647-6619","authenticated-orcid":true,"given":"Peizeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 400016"]},{"name":"The First Affiliated Hospital of Zhengzhou University, Henan International, Henan Province Eye Hospital , , ,","place":["Zhengzhou, China, 450052"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"2026081810302517900_cit1","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.preteyeres.2016.02.002","article-title":"Vogt-Koyanagi-Harada disease: Novel\ninsights into pathophysiology, diagnosis and treatment","volume":"52","author":"Du","year":"2016","journal-title":"Prog. 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