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Current anti\u2010inflammatory drugs for DED are limited by low bioavailability, ocular irritation, and inadequate relief. Herein, we propose a multifunctional hydrogel encapsulating Mizoribine, a small\u2010molecule water\u2010soluble immunosuppressant. The formulation undergoes in situ gelation on the ocular surface, forms a mucin\u2010adhered coating, and responds to pathological oxidative stress to enable controlled drug release. In vitro studies demonstrate the formulation effectively mitigates cellular oxidative stress by scavenging ROS and upregulating antioxidant factors. It also protects mitochondrial function, reduces apoptosis, and modulates macrophage polarization. In vivo, topical application of the hydrogel markedly alleviates clinical signs of disease. It also suppresses ocular surface inflammation and reverses conjunctival goblet cell loss. Molecular and cellular analyses indicate the hydrogel exerts its therapeutic effects primarily through antioxidative, anti\u2010inflammatory, and macrophage\u2010modulating mechanisms. Importantly, the formulation exhibits an excellent biosafety profile. Our findings highlight that this multifunctional hydrogel serves as a potent, convenient, and safe nanotherapeutic platform. By integrating ROS\u2010responsive, thermosensitive, and sustained drug\u2010release properties with antioxidant, anti\u2010inflammatory, and immunomodulatory functions, this formulation simultaneously targets multiple pathological pathways, offering a promising avenue for clinical translation in treating chronic ocular surface diseases.<\/jats:p>","DOI":"10.1002\/advs.78106","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:01:10Z","timestamp":1791352870000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A ROS\u2010Responsive and Mucoadhesive Thermosensitive Hydrogel Encapsulated with Mizoribine for Synergistic Dry Eye Therapy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4024-3870","authenticated-orcid":false,"given":"Danyi","family":"Qin","sequence":"first","affiliation":[{"name":"Xiamen University affiliated Xiamen Eye Center Fujian Provincial 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