Nanoscale Metal–Organic Framework Hierarchically Combines High-Z Components for Multifarious Radio-Enhancement

With tunability and porosity, nanoscale metal-organic frameworks (nMOFs) can incorporate multiple components to realize complex functions for biomedical applications. Here we report the synthesis of W₁₈@Hf₁₂-DBB-Ir, a new nMOF assembly hierarchically incorporating three high-Z components-Hf-based metal-oxo clusters, Ir-based bridging ligands, and W-based polyoxometalates (POMs)-as a multifarious radioenhancer. Cationic Hf₁₂-DBB-Ir was built from Hf₁₂ secondary building units (SBUs) and [Ir(bpy)₂(ppy)]⁺ (bpy = 2,2'-bipyridine, ppy = 2-phenylpyridine) derived dicarboxylate ligands (DBB-Ir) and then loaded with Wells-Dawson-type [P₂W₁₈O₆₂]^6- (W₁₈) POMs to afford W₁₈@Hf₁₂-DBB-Ir. Upon X-ray irradiation, W₁₈@Hf₁₂-DBB-Ir significantly enhances hydroxyl radical generation from Hf₁₂ SBUs, singlet oxygen generation from DBB-Ir ligands, and superoxide generation from W₁₈ POMs, respectively. Through synergistic cell killing by these distinct reactive oxygen species, W₁₈@Hf₁₂-DBB-Ir elicited superb anticancer efficacy with >98% tumor regression at a low X-ray dose of 5 × 1 Gy.