Remarkable Enhancement of the Radiotherapeutic Efficacy via Targeted Reduction of Hypoxic Conditions and Depletion of Intracellular Glutathione Utilizing Cu2–xSe@Pt Nanoplatforms

Integrating multifunctional nanostructures to improve tumor microenvironment-mediated radiotherapy (RT) resistance combined with photothermal ablation represents a novel approach to killing tumor cells. In this work, we developed a synergistic nanoplatform (Cu2–xSe@Pt, CS@Pt) capable of simultaneously addressing hypoxia, glutathione (GSH) overexpression, and energy deposition limitations. The mean lethal dose of radiation for KYSE30 tumor cells was significantly reduced by approximately 60% after CS@Pt incubation, decreasing from 4.92 to 1.97 Gy. Additionally, CS nanoparticles exhibit effective photothermal properties, enabling the CS@Pt formulation to integrate bioimaging with photothermal therapy (PTT) and RT, thereby creating a multifunctional nanoplatform for comprehensive tumor treatment. Both in vitro and in vivo experiments demonstrated that the combination of RT and PTT achieved complete tumor ablation, exhibiting excellent biosafety and potential for clinical translation.