Development of Ce-doped TiO₂ activated by X-ray irradiation for alternative cancer treatment

Photodynamic therapy (PDT) is limited by its penetration depth because of the selection of photosensitizer and light source. In this study, Ce-doped TiO₂ (TiO₂:Ce) was synthesized by a modified sol-gel method to act as a photosensitizer activated by low-dose X-rays, less harmful than ionizing radiation, to generate intracellular reactive oxygen species (ROS). The A549 cell line was used as the in vitro and in vivo model to evaluate the efficacy of X-ray-irradiated TiO₂:Ce to induce cell death. The cell viability significantly decreased with TiO₂:Ce exposure under low-dose X-ray irradiation. An LDH assay showed that intracellular TiO₂:Ce under X-ray irradiation was cytotoxic to A549 cancer cells. TiO₂:Ce produced significant ROS under low-dose X-ray irradiation and promoted apoptosis/necrosis of A549 cancer cells. TiO₂:Ce can enhance the efficacy of X-ray-induced PDT, and tumor growth was inhibited in vivo. The mechanisms underlying ROS generation by TiO₂:Ce activated by X-ray irradiation to induce cell toxicity, thereby inhibiting tumor growth, is discussed.