Delivering metal ions by nanomaterials: Turning metal ions into drug-like cancer theranostic agents

Nanomaterials have been extensively used for cancer therapy and diagnosis due to their designability, multifunctionality, and unique in vivo distribution. Metal ions are increasingly seen in cancer therapy and diagnostics as more and more biological effects of metal ions are revealed. Metal-ion-based antitumor strategies, as well as metal-ion-based designed nanomaterials, are continuously being developed with exciting and emerging impacts. Meanwhile, metal-ion-based nanomaterials are forming drug-free theranostic nanoplatforms, where metal ions, as part of building nanomaterials, replace conventional drugs. In this review, we discuss recent advances in multi-functional designed nanomaterials with the ability to deliver metal ions and focus on the role of metal ions in cancer therapy, including chemotherapy, chemodynamic therapy, immunotherapy, etc. The metal-ion-induced cell death, such as apoptosis, ferroptosis, and cuproptosis, is detailed in this review. Mono-/Multi-model imaging depending on metal ions for tumor diagnosis and guided tumor treatment is also the emphasis. By discussing the applications, challenges, and opportunities, we expect the metal-ions-based theranostic nanoplatforms have a far-reaching development in preclinic or clinics.