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Here, a nanofiber\u2010based drug delivery system (5F\/STFM\/R\u2010ES) is developed that synergistically induces ferroptosis and potentiates immunotherapy to inhibit melanoma growth and reduce the risk of metastasis and recurrence. To this end, mesoporous silica nanoparticles encapsulating resiquimod (R848) are surface\u2010coated with Fe\/Mn\u2010based metal\u2010polyphenol networks (TFM) to form STFM\/R. Subsequently, STFM\/R is electrospun into 5\u2010fluorouracil\u2010loaded nanofibers. When applied to the tumor site, 5\u2010fluorouracil and STFM\/R are released. Following the degradation of STFM\/R, the release of Fe\n                    <jats:sup>2<\/jats:sup>\n                    \u207a triggered ferroptosis through iron overload, while the simultaneous liberation of Mn\n                    <jats:sup>2<\/jats:sup>\n                    \u207a synergizes with R848 to activate the cGAS\u2010STING signaling pathway. This multifunctional strategy promotes the maturation of dendritic cells and repolarizes tumor\u2010associated macrophages from M2 to M1. The in vivo and in vitro evaluations reveal that 5F\/STFM\/R\u2010ES significantly improves delivery efficacy, remodels the immunosuppressive tumor microenvironment, and enhances the therapeutic efficacy of chemotherapeutics. The localized delivery strategy of the platform minimizes systemic toxicity while achieving combinatorial therapeutic effects, highlighting its potential for personalized melanoma therapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202508753","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T14:52:13Z","timestamp":1760971933000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Nanoparticle\u2010Modified Nanofibers Induce Ferroptosis and Stimulate Antitumor Immunity for Melanoma Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Mingyang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Stomatology Shandong Provincial Hospital Affiliated to Shandong First Medical University  No.324 Jingwuweiqi Road, Huaiyin District Jinan Shandong Province 250021 P. R. 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