Pharmacological Ascorbate Promotes the Tumor Radiosensitization of Au@Pd Nanoparticles with Simultaneous Protection of Normal Tissues

Nanoradiosensitizers containing high-Z elements hold great potential in radiotherapy owing to the increasing energy deposition effect on X-ray irradiation. However, their potential clinical application is limited by the irradiation damage in nontarget tissues surrounding the tumor site, as well as the safety concerns for nanomaterials. Our findings demonstrate that pharmacological ascorbate displays a synergistic radiosensitizing effect in combination with nanoradiosensitizers. By engineering the Au@Pd core–shell nanostructures and precisely regulating their shell thickness, the obtained Au@Pd nanomaterials exhibit excellent ascorbate oxidase-like activity. Along with the accelerating generation of H₂O₂, pharmacological ascorbate significantly enhances the radiosensitizing effect of Au@Pd-PEG nanoparticles on both cancer cells and solid tumor. Interestingly, pharmacological ascorbate effectively protects normal tissues from X-ray-induced injury. The present work demonstrates that pharmacological ascorbate is an ideal agent for selectively improving the radiosensitizing effect of nanomaterials, providing a promising strategy to facilitate the clinical translation of nanoradiosensitizers.