Engineering the bandgap of TiO2 nanorods through copper doping: a dual-modal strategy for radiosensitization and cuproptosis activation

Although titanium dioxide (TiO 2 ) semiconductor nanomaterials have garnered considerable attention in radiotherapy research due to their photoelectric effect, the inefficient electron-hole (e – -h + ) separation limits reactive oxygen species (ROS) generation upon X-ray irradiation in the tumor microenvironment (TME), restricting the therapeutic effect. Herein, we doped TiO 2 nanorods with various transition metals (Mn, Fe, Co, and Cu) to tailor their bandgap structures. Among these, Cu-doped TiO 2 nanorods (Cu-TiO 2 NRs) demonstrated the most outstanding performance during radiotherapy. On one hand, the incorporation of Cu in TiO 2 narrows the bandgap, enhances e⁻-h⁺ separation, and promotes ROS generation under irradiation. Meanwhile, Cu 2+ on the surface can act as traps to capture photoelectrons, converting into Cu + with Fenton-like reactivity, boosting ROS level in the TME. What’s more, the accumulated Cu + effectively induced cuproptosis in tumor cells, thereby overcoming tumor radioresistance and enhancing the therapeutic effect. Both in vitro and in vivo experiments demonstrated that Cu-TiO 2 NRs combined with low-dose X-ray irradiation significantly inhibited tumor growth. These findings establish copper-doping engineering as a promising strategy for achieving synergistic cancer therapy by integrating radiotherapy with cuproptosis induction, offering a safe and effective approach for clinical translation.