biostudies-literatureZhen WLudwig Institute for Metastasis ResearchNCI NIH HHSNational Institutes of HealthUniversity of Chicago Medicine Comprehensive Cancer CenterNIH HHSe2405494https://www.ebi.ac.uk/biostudies/studies/S-EPMC11891090biostudies-literatureUnknown37(52)The efficacy of radiotherapy (RT) is limited by inefficient X-ray absorption and reactive oxygen species generation, upregulation of immunosuppressive factors, and a reducing tumor microenvironment (TME). Here, the design of a mitochondria-targeted and digitonin (Dig)-loaded nanoscale metal-organic framework, Th-Ir-DBB/Dig, is reported to overcome these limitations and elicit strong antitumor effects upon low-dose X-ray irradiation. Built from Th₆O₄(OH)₄ secondary building units (SBUs) and photosensitizing Ir(DBB)(ppy)₂ ²⁺ (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 radicalAdvanced materials (Deerfield Beach, Fla.)Digitonin-Loaded Nanoscale Metal-Organic Framework for Mitochondria-Targeted Radiotherapy-Radiodynamic Therapy and Disulfidptosis.PMC11891090NIH CCSG: P30 CA014599R01 CA253655P30 CA0145991R01CA253655Blenko ALGermanas TZhen WLi JFan YTillman LLin WWeichselbaum RRfalseDigitonin-Loaded Nanoscale Metal-Organic Framework for Mitochondria-Targeted Radiotherapy-Radiodynamic Therapy and Disulfidptosis.The efficacy of radiotherapy (RT) is limited by inefficient X-ray absorption and reactive oxygen species generation, upregulation of immunosuppressive factors, and a reducing tumor microenvironment (TME). Here, the design of a mitochondria-targeted and digitonin (Dig)-loaded nanoscale metal-organic framework, Th-Ir-DBB/Dig, is reported to overcome these limitations and elicit strong antitumor effects upon low-dose X-ray irradiation. Built from Th₆O₄(OH)₄ secondary building units (SBUs) and photosensitizing Ir(DBB)(ppy)₂ ²⁺ (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 radical2025-01-01T00:00:00Z2025 Dec2026-06-14T03:09:52.126Z2026-06-14T03:08:08.685ZS-EPMC118910903925268810.1002/adma.202405494