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Heterojunction formation promoted interfacial charge redistribution, with approximately 1.942 electrons transferred from Cu2S to FeSnO(OH)5, and reduced the calculated energy barrier of the rate-determining peroxidase-like step from 2.38 to 2.03 eV. Consequently, FCS enhanced ultrasound-triggered singlet oxygen and hydroxyl radical generation, peroxidase-like catalysis, and glutathione depletion, thereby amplifying oxidative stress. The microneedles enabled efficient skin penetration and acidity-responsive delivery, releasing approximately 80% of phloretin at pH 5.4 vs 40% at pH 7.4 within 80 min, while ultrasound accelerated tip dissolution. In 4T1 cells, FCS and phloretin (FCSP) combined with ultrasound induced pronounced oxidative and mitochondrial damage accompanied by ferroptosis- and cuproptosis-associated responses, including lipid peroxidation, glutathione peroxidase 4 suppression, and dihydrolipoamide S-acetyltransferase oligomerization. In 4T1 tumor-bearing mice, FCSP-MN plus ultrasound achieved the strongest tumor-growth suppression among the tested treatments, with stable body weight and no obvious histological injury to major organs. This platform couples heterointerface-enhanced redox catalysis, responsive local delivery, and Fe\/Cu dyshomeostasis for multimodal tumor therapy.<\/jats:p>","DOI":"10.1021\/acsami.6c16298","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:02:24Z","timestamp":1789970544000},"page":"52203-52218","source":"Crossref","is-referenced-by-count":0,"title":["Ultrasound-Activated FeSnO(OH)5\/Cu2S Heterojunction Microneedles Coordinate Redox Catalysis and Metal-Ion Dyshomeostasis for Localized Tumor Therapy"],"prefix":"10.1021","volume":"18","author":[{"given":"Zhuo","family":"Xiao","sequence":"first","affiliation":[{"name":"Harbin Normal University , , ,","place":["Harbin, China, 150025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexin","family":"Li","sequence":"additional","affiliation":[{"name":"Harbin Normal University , , ,","place":["Harbin, China, 150025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3062-1434","authenticated-orcid":true,"given":"Chunyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Harbin Normal University , , ,","place":["Harbin, China, 150025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengshu","family":"Xu","sequence":"additional","affiliation":[{"name":"Harbin Normal University , , ,","place":["Harbin, China, 150025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoran","family":"Yang","sequence":"additional","affiliation":[{"name":"Harbin Normal University , , ,","place":["Harbin, China, 150025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5445-7872","authenticated-orcid":true,"given":"Wei","family":"Guo","sequence":"additional","affiliation":[{"name":"Harbin Normal University , , ,","place":["Harbin, China, 150025"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"issue":"6","key":"2026093001072404000_cit1","doi-asserted-by":"publisher","DOI":"10.1002\/exp.20240188","article-title":"Multi-energy integrated photocatalysis for antitumor therapy","volume":"5","author":"Zhang","year":"2025","journal-title":"Exploration"},{"issue":"9","key":"2026093001072404000_cit2","doi-asserted-by":"publisher","first-page":"E1525","DOI":"10.1016\/s2214-109x(25)00264-5","article-title":"Global burden of cancer attributable to HIV: A worldwide incidence analysis","volume":"13","author":"Huang","year":"2025","journal-title":"Lancet Glob. 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