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This study presents such nanotheranostic platform (<jats:sup>177<\/jats:sup>Lu\u2010MFeCu@Tan) via co\u2010assembling <jats:sup>177<\/jats:sup>Lu radionuclide and tanshinone (Tan) into Fe\/Cu dual\u2010metal nanozyme (MFeCu). This platform simultaneously enables single\u2010photon emission computed tomography (SPECT) imaging and a quadruple\u2010synergistic tumor therapy approach, including internal radioisotope therapy (RIT), catalysis therapy, chemotherapy, and MFeCu\u2010mediated ferroptosis and cuproptosis therapy. In this platform, the MFeCu can catalyze excessive intracellular hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) to generate radical oxygen species (ROS) and deplete glutathione (GSH). The excess of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> and GSH are main factors for radioresistance and chemoresistance, reducing them can enhance chemotherapy and RIT. The generated ROS and depleted GSH further induce mitochondrial dysfunction and promote the aggregation of lipoylated dihydrolipoamide S\u2010acetyltransferase and lipid peroxidation, causing the enhance of ferroptosis and cuproptosis. The in vitro and in vivo results demonstrate that this quadruple\u2010synergistic approach shows significant therapeutic efficacy to complete tumor eradication and reduced recurrence in vivo. In conclusion, this work presents a promising strategy for designing SPECT imaging\u2010guided quadruple\u2010synergistic therapy and highlights the feasibility of developing a self\u2010assembled radionuclide and small molecule chemotherapy drugs nanotherapeutic platform for combined treatment of cancer.<\/jats:p>","DOI":"10.1002\/adhm.202402696","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:14:31Z","timestamp":1731629671000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Fe\/Cu Bimetallic Nanozyme Co\u2010Assembled with <sup>177<\/sup>Lu and Tanshinone for Quadruple\u2010Synergistic Tumor\u2010Specific Therapy"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5594-6256","authenticated-orcid":false,"given":"Xianyu","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine Beijing Friendship Hospital 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