Digitonin‐Loaded Nanoscale Metal–Organic Framework for Mitochondria‐Targeted Radiotherapy‐Radiodynamic Therapy and Disulfidptosis

(Ir-DBB, DBB = 4,4'-di(4-benzoato)-2,2'-bipyridine; ppy = 2-phenylpyridine) ligands, Th-Ir-DBB exhibits strong RT-radiodynamic therapy (RDT) effects via potent radiosensitization with high-Z SBUs for hydroxyl radical generation and efficient excitation of Ir-DBB ligands for singlet oxygen production. Th-Ir-DBB/Dig releases digitonin in acidic TMEs to trigger disulfidptosis of cancer cells and sensitize cancer cells to RT-RDT through glucose and glutathione depletion. The released digitonin simultaneously downregulates multiple immune checkpoints in cancer cells and T cells through cholesterol depletion. As a result, Th-Ir-DBB/dig plus X-ray irradiation induces strong antitumor immunity to effectively inhibit tumor growth in mouse models of colon and breast cancer.