Oxygen Vacancy‐Rich Manganese Nanoflowers as Ferroptosis Inducers for Tumor Radiotherapy

Abstract The combination of ferroptosis and innovative tumor therapy methods offers another promising answer to the problem of tumors. In order to generate effective ferroptosis in tumor cells, iron‐based nanomaterials are commonly utilized to introduce foreign iron as a trigger for ferroptosis. However, this usually necessitates the injection of larger doses of iron into the body. These exogenous iron increases are likely to create concealed concerns for symptoms such as liver damage and allergy. Herein, an iron‐free radiosensitizer is introduced, oxygen‐vacancy‐rich MnO 2 nanoflowers ( ovs ‐MnO 2 ), that promotes ferroptosis and modifies the tumor microenvironment to assist radiotherapy. ovs ‐MnO 2 with enriched oxygen vacancies on the surface induces the release of intracellular free iron (Fe 2+ ), which functions as an activator of Fenton reaction and enhances the accumulation of intracellular reactive oxygen species. On the other hand, Fe 2+ also triggers the ferroptosis and promotes the accumulation of lipid peroxides. Subsequently, the depletion of glutathione and accumulation of lipid peroxidation in tumor cells leads to the inactivation of glutathione peroxidase 4 (GPX4) and ferroptosis, thereby enhancing the therapeutic efficacy of radiotherapy. The nanoplatform provides a novel strategy for generating novel nanomedicines for ferroptosis‐assisted radiotherapy.