Nanoscale Metal-Organic Layers for Radiotherapy-Radiodynamic Therapy

Nanoscale metal-organic layers (nMOLs) are an emerging class of 2D crystalline materials formed by reducing the dimensionality of nanoscale metal-organic frameworks (nMOFs). nMOLs hold significant potential in biomedical applications by combining the structural and compositional tunability of nMOFs and anisotropic properties of 2D nanomaterials. Here we report two novel nMOLs, Hf-12-Ir and Hf-6-Ir, based on Hf-12 and Hf-6 secondary building units (SBUs) and photosensitizing Ir(bpy)[dF(CF3)ppy](2)(+) derived ligands [bpy = 2,2'-bipyridine; dF(CF3)ppy = 2-(2,4-difluorophenyl)-5-(trifluoromethyl)pyridine] for radiotherapy (RT) and radiodynamic therapy (RDT). Upon X-ray irradiation, the Hf-12 or Hf-6 SBUs in the nMOLs efficiently absorb X-rays to enhance RT by producing hydroxyl radicals and to elicit RDT through the excitation of Ir(bpy)[dF(CF3)ppy](2)(+) derived ligands to generate singlet oxygen and superoxide anions. Hf-12-Ir and Hf-6-Ir promoted effective cell instant death through RDT and cell reproductive death through RT to elicit superb anticancer efficacy, resulting in >99% tumor regression at low X-ray doses of 0.5 X 5 Gy.