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As a newly defined mode of cell death regulation, the mechanisms of copper efflux and high intracellular levels of reducing substances may impair cuproptosis efficacy. To address this, a nanocomposite designated POM\/Cu\u2010SS@HA was constructed, comprising sandwich\u2010type polyoxometalate (POM) Na[(CH\n                    <jats:sub>3<\/jats:sub>\n                    )\n                    <jats:sub>2<\/jats:sub>\n                    NH\n                    <jats:sub>2<\/jats:sub>\n                    ]\n                    <jats:sub>13<\/jats:sub>\n                    H[Sc\n                    <jats:sub>3<\/jats:sub>\n                    (H\n                    <jats:sub>2<\/jats:sub>\n                    O)\n                    <jats:sub>2<\/jats:sub>\n                    Te\n                    <jats:sub>2<\/jats:sub>\n                    W\n                    <jats:sub>24<\/jats:sub>\n                    O\n                    <jats:sub>90<\/jats:sub>\n                    ]\u00b792H\n                    <jats:sub>2<\/jats:sub>\n                    O (\n                    <jats:bold>\n                      Sc\n                      <jats:sub>3<\/jats:sub>\n                      Te\n                      <jats:sub>2<\/jats:sub>\n                      W\n                      <jats:sub>24<\/jats:sub>\n                    <\/jats:bold>\n                    ), disulfide\u2010bridged copper\u2010based complexes (Cu\u2010SS), and hyaluronic acid (HA) for targeted delivery. This system induces cuproptosis through copper accumulation, leading to lipoylated protein aggregation and iron\u2013sulfur cluster protein depletion, while concurrently facilitating photothermal therapy (PTT) and apoptosis. The POM (\n                    <jats:bold>\n                      Sc\n                      <jats:sub>3<\/jats:sub>\n                      Te\n                      <jats:sub>2<\/jats:sub>\n                      W\n                      <jats:sub>24<\/jats:sub>\n                    <\/jats:bold>\n                    ) cluster exhibited potent antitumor effects via p53\u2010dependent apoptotic pathway reactivation. In vitro studies demonstrated over 85.6% inhibition rate against 4T1 breast cancer cells when combining POM\/Cu\u2010SS@HA with 808\u00a0nm NIR irradiation. In vivo results showed 92.8% tumor growth suppression compared to the controls. Transcriptome analysis further identified altered expression profiles in glutathione (GSH) metabolism and mitochondrial function\u2010related genes, confirming the dual induction of cuproptosis and apoptosis. These findings establish a synergistic nanotherapeutic strategy with enhanced efficacy for breast cancer treatment.\n                  <\/jats:p>","DOI":"10.1002\/anie.202514795","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T04:24:12Z","timestamp":1761020652000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tungstotellurate(VI)\u2010Based Nanocomposite Inhibits Breast Cancer Proliferation and Metastasis by Enhancing Cuproptosis and Apoptosis"],"prefix":"10.1002","volume":"64","author":[{"given":"Mo","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmacy National Key Laboratory of New Pharmaceutical Preparations and Excipients Key Laboratory of Innovative Drug Development and Evaluation Hebei Medical University  Shijiazhuang 050017 P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siao","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy National Key Laboratory of New Pharmaceutical Preparations and Excipients Key Laboratory of Innovative Drug Development and Evaluation Hebei Medical University  Shijiazhuang 050017 P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Hebei Technology Innovation Center for Energy Conversion Materials and Devices College of Chemistry and Materials Science Hebei Normal University  Shijiazhuang 050024 P.R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9628-6888","authenticated-orcid":false,"given":"Zhengguo","family":"Lin","sequence":"additional","affiliation":[{"name":"Hebei Technology Innovation Center for Energy Conversion Materials and Devices College of Chemistry and Materials Science Hebei Normal University  Shijiazhuang 050024 P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy National Key Laboratory of New Pharmaceutical Preparations and Excipients Key Laboratory of Innovative Drug Development and Evaluation Hebei Medical University  Shijiazhuang 050017 P.R. 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