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Effective yet safe therapeutics for severe DED are still highly demanded. Herein, considering the important role of excessive reactive oxygen species (ROS) in triggering DED, an eye\u2010drop nano\u2010formulation of catalase (CAT) self\u2010assembled with cysteine\u2010modified chitosan (CS\u2010Cys) is designed for DED treatment. Upon eye\u2010drop administration of CS\u2010Cys\/CAT nanoparticles, CS\u2010Cys can form disulfide bonds with abundant thiols in the mucin layer of the tear film, anchoring catalase to the corneal surface. Thus the excess ROS accumulated on the ocular surface can be effectively eliminated, resulting in a regulated tear microenvironment. In mouse and rabbit models, it is verified that CS\u2010Cys\/CAT eye drops can offer excellent therapeutic effects, especially in promoting the recovery of damaged epithelium and increasing tear secretion. Remarkably, CS\u2010Cys\/CAT eye drops showed notably better therapeutic performance than clinically used cyclosporin and dexamethasone, as well as several new DED drugs in clinical trials. Thus, the work presents a unique nanoparticulate eye\u2010drop\u2010based ocular delivery system to allow prolonged ocular retention of protein therapeutics, and such nanoformulation formulated by fully biocompatible\/biodegradable components possesses significant translational potential for effective and safe DED treatment.<\/jats:p>","DOI":"10.1002\/adma.202415353","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T04:06:48Z","timestamp":1742789208000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Eye\u2010Drop Nano\u2010Formulation of Catalase Self\u2010Assembled with Thiolated Chitosan for Effective Treatment of Dry Eye Disease"],"prefix":"10.1002","volume":"37","author":[{"given":"Ming","family":"Shao","sequence":"first","affiliation":[{"name":"Institute of Functional Nano &amp; Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon\u2010Based Functional Materials &amp; Devices Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chai","sequence":"additional","affiliation":[{"name":"InnoBM Pharmaceuticals Co. 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