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Herein, two iron\u2010chelating and reactive oxygen species (ROS)\u2010scavenging polymers with thioketal and thioester bonds delivering Lip\u20101 are designed and self\u2010assembled into NPs\n                    <jats:sup>Lip\u20101<\/jats:sup>\n                    , which pose a triple threat to RGC of Acute Glaucoma via ROS scavenging, iron ion chelation, and potent ferroptosis inhibition. Upon immediate cellular uptake of NPs\n                    <jats:sup>Lip1<\/jats:sup>\n                    by RGCs, the elevated intracellular ROS triggers the cleavage of thioether bonds and the oxidation of thioester bonds, resulting in ROS consumption and simultaneous release of Lip\u20101 and exposure of polymer chains with pendant 1,4,7\u2010triazacyclononane\u20101,4,7\u2010triacetic acid (NOTA) groups. On the one hand, the NOTA groups can chelate with iron ions, thereby inhibiting ferroptosis in RGCs. On the other hand, the released Lip\u20101 can inhibit ferroptosis by upregulating glutathione peroxidase 4 (GPX4). Together, NPs\n                    <jats:sup>Lip\u20101<\/jats:sup>\n                    with a triple threat markedly reduced ferroptosis and oxidative stress, significantly enhancing the survival of R28 cells. Further, NPs\n                    <jats:sup>Lip\u20101<\/jats:sup>\n                    effectively inhibits the RGC ferroptosis and preserves the visual function. Overall, the findings indicated NPs\n                    <jats:sup>Lip\u20101<\/jats:sup>\n                    provides substantial protection for RGCs via suppressing oxidative stress and ferroptosis, representing a promising therapeutic avenue for glaucoma.\n                  <\/jats:p>","DOI":"10.1002\/adma.202507526","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T06:51:41Z","timestamp":1752216701000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Iron\u2010Chelating and ROS\u2010Scavenging Polymers with Thioketal and Thioether Bonds Delivering Ferroptosis Inhibitor Lip\u20101 Provide a Triple Therapeutic Strategy for Retina Ganglion Cells in Acute Glaucoma"],"prefix":"10.1002","volume":"37","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Molecular Medicine Hangzhou Institute for Advanced Study  Hangzhou 310013 P. R. China"},{"name":"University of Chinese Academy of Sciences  Beijing 100049 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Hunan Key Laboratory of Ophthalmology Xiangya Hospital Central South University  Changsha Hunan 410008 P. R. China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganghao","family":"Liang","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences  Beijing 100049 P. R. China"},{"name":"Beijing National Laboratory for Molecular Sciences Laboratory of Polymer Physics and Chemistry Institute of Chemistry Chinese Academy of Sciences  Beijing 100190 P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Hunan Key Laboratory of Ophthalmology Xiangya Hospital Central South University  Changsha Hunan 410008 P. R. China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 P. R. China"},{"name":"Department of Ophthalmology Changde Hospital Xiangya School of Medicine Central South University (The first people's hospital of Changde city)  Changde Hunan 415000 P. R. 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