{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T01:27:08Z","timestamp":1788830828727,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"32","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071002"],"award-info":[{"award-number":["82071002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271057"],"award-info":[{"award-number":["82271057"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371105"],"award-info":[{"award-number":["82371105"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Uveal melanoma (UM) is a highly therapy\u2010resistant ocular malignancy with an immunosuppressive tumor microenvironment (TME) and low tumor mutational burden. Here, we developed NP@Fla\u2010Cu, a glutathione (GSH)\u2010responsive nanoparticle designed to co\u2010induce cuproptosis and mitophagy dysregulation. Cuproptosis, a copper\u2010dependent mitochondrial cell death pathway, is amplified by NP@Fla\u2010Cu's dual functionality: its GSH\u2010degradable shell depletes copper\u2010chelating GSH, while its core delivers a flavopiridol\u2010copper complex (Fla\u2010Cu). Flavopiridol acts as a copper ionophore, driving mitochondrial copper overload to trigger cuproptosis, while hyperactivating mitophagy, causing organelle depletion and metabolic collapse. In UM intraocular orthotopic xenograft models, NP@Fla\u2010Cu exhibited tumor\u2010specific accumulation and potent antitumor activity. Immunological evaluation in a B16F10 murine melanoma model further demonstrated that NP@Fla\u2010Cu effectively remodeled the tumor immune microenvironment, as evidenced by enhanced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration. By synergizing copper cytotoxicity with immunomodulation, this nanoplatform sensitizes immune\u2010cold UM to immunotherapy. This work establishes cuproptosis induction via NP@Fla\u2010Cu as a transformative strategy against UM, effectively addressing challenges in tumor selectivity and off\u2010target toxicity. The dual functionality of flavopiridol as a copper ionophore and mitophagy activator provides a promising combinatorial approach to overcome therapy resistance in immunosuppressive malignancies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202521183","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:31:21Z","timestamp":1774618281000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dual\u2010Targeting Cuproptosis and Mitophagy via a Flavopiridol\u2010Copper Nanoplatform Potentiates Immunotherapy Against Uveal Melanoma"],"prefix":"10.1002","volume":"13","author":[{"given":"Hong","family":"Ren","sequence":"first","affiliation":[{"name":"Eye Center of Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Hunan Key Laboratory of Ophthalmology Central South University  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric 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