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The approval of various metallodrugs for tumor therapy brings more attention to the antitumor effect of metal ions. With the deepening understanding of the regulation mechanisms of metal ion homeostasis in vivo, breaking intracellular metal ion homeostasis becomes a new means to inhibit the proliferation of tumor cells and activate antitumor immune response. Diverse nanomedicines with the loading of small molecular ion regulators or metal ions have been developed to disrupt metal ion homeostasis in tumor cells, with higher safety and efficiency than free small molecular ion regulators or metal compounds. This comprehensive review focuses on the latest progress of various intracellular metal ion homeostasis regulation\u2010based nanomedicines in tumor therapy including calcium ion (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ), ferrous ion (Fe\n                    <jats:sup>2+<\/jats:sup>\n                    ), cuprous ion (Cu\n                    <jats:sup>+<\/jats:sup>\n                    ), managanese ion (Mn\n                    <jats:sup>2+<\/jats:sup>\n                    ), and zinc ion (Zn\n                    <jats:sup>2+<\/jats:sup>\n                    ). The physiological functions and homeostasis regulation processes of ions are summarized to guide the design of metal ion regulation\u2010based nanomedicines. Then the antitumor mechanisms of various ions\u2010based nanomedicines and some efficient synergistic therapies are highlighted. Finally, the challenges and future developments of ion regulation\u2010based antitumor therapy are also discussed, hoping to provide a reference for finding more effective metal ions and synergistic therapies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202306203","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T11:52:03Z","timestamp":1702036323000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Nanoenabled Intracellular Metal Ion Homeostasis Regulation for Tumor Therapy"],"prefix":"10.1002","volume":"11","author":[{"given":"Lihua","family":"Xu","sequence":"first","affiliation":[{"name":"Sino\u2010British Research Centre for Molecular Oncology National Centre for International Research in Cell and Gene Therapy State Key Laboratory of Esophageal Cancer Prevention &amp; Treatment School of Basic Medical Sciences Academy of Medical Sciences Zhengzhou University  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