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

Int J Mol Sci. 2019 Mar 6;20(5):1148. doi: 10.3390/ijms20051148.

Abstract

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.

Keywords: X-ray; alternative tumor treatment; calcium carbonate; cerium.

MeSH terms

  • A549 Cells
  • Animals
  • Calcium Carbonate / administration & dosage*
  • Calcium Carbonate / chemistry
  • Calcium Carbonate / pharmacology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cerium / chemistry*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Mice
  • Photochemotherapy / methods*
  • Reactive Oxygen Species / metabolism*
  • X-Rays
  • Xenograft Model Antitumor Assays

Substances

  • Reactive Oxygen Species
  • Cerium
  • Calcium Carbonate