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However, conventional cfDNA scavengers have limited blood\u2010retinal barrier penetration, and monotherapies cannot control the complex inflammatory network. Herein, we developed a cationic poly(disulfide)\u2010drug nanoplatform (LA\/DexP), which self\u2010assembled via salt bridge interactions and aggregation\u2010induced polymerization between a guanidyl\u2010functionalized lipoic acid derivative (LA) and dexamethasone phosphate (DexP). This platform is designed to synergistically inhibit the cGAS\u2010STING pathway and achieve efficient intraocular drug delivery. LA\/DexP functioned as an efficient scavenger of cfDNA through electrostatic interaction, thereby inhibiting cGAS\u2010STING overactivation. Meanwhile, it leveraged thiol\u2010disulfide exchange to enhance blood\u2010retinal barrier penetration, achieving a 5.09\u2010fold higher apparent permeability coefficient than free DexP, and exhibited ROS\u2010responsive drug release. In an experimental autoimmune uveitis mouse model, LA\/DexP treatment significantly reduced cfDNA levels and inhibited cGAS\u2010STING signaling. It also downregulated pro\u2010inflammatory cytokine expression, promoted macrophage polarization from the pro\u2010inflammatory M1 to the anti\u2010inflammatory M2 phenotype, and rebalanced Th1\/Th17\u2010Treg cell subsets. These combined effects effectively inhibited uveitis severity. In summary, this study establishes a highly barrier\u2010permeable nanoplatform that synergistically integrates drug delivery with cGAS\u2010STING pathway inhibition, offering a promising therapeutic strategy for autoimmune uveitis.<\/jats:p>","DOI":"10.1002\/advs.76813","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:31:37Z","timestamp":1785328297000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Aggregation\u2010Induced Polymerization Poly(Disulfide)\u2010Drug Nanoplatform for Autoimmune Uveitis Therapy via Inhibiting the cGAS\u2010STING Pathway"],"prefix":"10.1002","volume":"13","author":[{"given":"Yuelan","family":"Wu","sequence":"first","affiliation":[{"name":"Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory For the Prevention and Treatment of Major Blinding Eye Diseases Chongqing Branch 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