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.