Copper Oxide Nanoparticles Induce Enhanced Radiosensitizing Effect via Destructive Autophagy

Emerging nanotechnologies for radiotherapy are attracting increasing interest from researchers in recent years. To improve the radiotherapeutic performance, developing nanoparticles that can efficiently generate toxic reactive oxygen species (ROS) under X-ray irradiation are highly desirable. Here, we investigate the potential of copper oxide nanoparticles (CuO NPs) as nanoradiosensitizers. Increased cancer cell inhibition is observed in colony formation assay and real-time cell analysis after the combined treatment with CuO NPs and X-ray irradiation, whereas the CuO NPs alone do not have any negative influence on cell viability, indicating the radiosensitization effect of CuO NPs. Importantly, the significantly increased ROS level in cells contributes to the enhanced damage to cancer cells under the combined treatment. Besides, the cell cycle is regulated to the X-ray-sensitive phase (G₂/M phase) by CuO NPs, which may also account for the inhibited proliferation of cancer cells. Furthermore, results from Western blot analysis and colony formation assay reveal that the increased cell death may be mainly attributed to the excessive autophagy induced by both CuO NPs and X-ray irradiation. Moreover, in vivo experiments verify the radiosensitization of CuO NPs and their favorable biosafety. The current study suggests that CuO NPs can be utilized as nanoradiosensitizers for increasing the efficiency of cancer radiotherapy.