Rare-Earth-Doped Calcium Carbonate Exposed to X-ray Irradiation to Induce Reactive Oxygen Species for Tumor Treatment

Conventional photodynamic therapy (PDT) is limited by its penetration depth due to the photosensitizer and light source. In this study, we developed X-ray induced photodynamic therapy that applied X-ray as the light source to activate Ce-doped CaCO₃ (CaCO₃:Ce) to generate an intracellular reactive oxygen species (ROS) for killing cancer cells. The A549 cell line was used as the in vitro and in vivo model to evaluate the efficacy of X-ray-induced CaCO₃:Ce. The cell viability significantly decreased and cell cytotoxicity obviously increased with CaCO₃:Ce exposure under X-ray irradiation, which is less harmful than radiotherapy in tumor treatment. CaCO₃:Ce produced significant ROS under X-ray irradiation and promoted A549 cancer cell death. CaCO₃:Ce can enhance the efficacy of X-ray induced PDT, and tumor growth was inhibited in vivo. The blood analysis and hematoxylin and eosin stain (H & E) stain fully supported the safety of the treatment. The mechanisms underlying ROS and CO₂ generation by CaCO₃:Ce activated by X-ray irradiation to induce cell toxicity, thereby inhibiting tumor growth, is discussed. These findings and advances are of great importance in providing a novel therapeutic approach as an alternative tumor treatment.