Au6Cu2 Clusters with High Electron Affinity and Oxygen-Mimetic Properties for Hypoxic Tumor Radiosensitization.

Hypoxia-induced radioresistance primarily contributes to the failure of radiotherapy because it hinders the effective fixation of DNA damage. Despite the considerable antitumor activity of chemical molecules such as electron-affinic nitroimidazoles affirmed by clinical studies, their dose-dependent side effects and low radiotherapy efficacy have become major drawbacks. In this study, we synthesized nitrobenzene-functionalized Au6Cu2 (NO2-Au6Cu2) clusters, integrating metal clusters with chemical radiosensitizers. Our findings indicate that the electron affinity of interfacial ligands has a significant effect on the electron affinity and hypoxic cytotoxicity of metal clusters. Experimental results demonstrated that NO2-Au6Cu2 clusters exhibit a high sensitization enhancement ratio by leveraging the properties of gold clusters to augment radiotherapy and the oxygen-mimetic property of chemical molecules to fix DNA damage. This research introduces a novel strategy for developing highly efficient metal cluster-based hypoxic radiosensitizers.