Radiosensitization effect of ZnO nanoparticles in lung cancer cells at clinically relevant megavoltage energy

Introduction: Radiation therapy is one of the major modalities that have long been used in cancer treatment. Radiotherapy is often accompanied by early and late toxicity and side effects and narrow therapeutic window. Similarity in radiation absorption properties of tumors and neighboring healthy tissues is often the reason for low specificity of radiation therapy. Development of nanomaterials for localized energy deposition under irradiation can increases radiation absorption by cancer tissue, expanding the therapeutic window and, thus, increasing specificity and efficacy of the treatment. ZnO nanoparticle is a wide band gap semiconductor with photo-oxidizing capacity under uv radiation. Recent studies have investigated photo-oxidizing under kilovoltage x-ray energy named as radiosensitization. The purpose of this study was to assess ZnO radiosensitization at clinically relevant MV X-ray energy.     Materials and Methods: ZnO nanoparticles with mean size of 10 nm were synthetized by a chemical precipitation method. The size, morphology and crystalline structure of the nanoparticles were characterized using transmission electron microscopy (TEM) and X-ray diffraction (XRD), respectively. The cytotoxicity of ZnO nps was evaluated on SKLC-6 lung cancer cell line by cell proliferation assay. The effect of ZnO nps on cell radiosensitivity under 6MV energy x-ray irradiation was evaluated using colonogenic assay. Mode of cell death was evaluated by flow cytometry.   Results: TEM images showed spherical ZnO NPs with narrow size distributions were synthesized. XRD pattern of purely synthesized NPs exhibited seven reflection peaks that can be indexed to the ZnO wurtzite structure. ZnO NPs were cytotoxic to the SKLC-6 cells in a dose-dependent manner as cell viability was decrease with the increase concentrations of ZnO nps. When comparing the radiation effects between the nanoparticle-containing and nanoparticle-free samples, the calculated radiation enhancement ratio of about 1.35-fold was achieved. FLow cytometry analysis confirmed that ZnO NPs, irradiation and combination of two induce apoptosis in SKLC-6 cells.   Conclusion: The potential of the ZnO nanoparticles for radiosensitization at MV energy was demonstrated in human lung cancer cell line (SKLC-6). Nanoparticle-mediated Enhancement Ratio was 1.35. Radiosensitizing effect can be attributed to X-ray-induced radiocatalysis by the nanoparticles at MV energy. Further development of ZnO nps might provide a new useful tool for research and clinical therapy in the field of oncology.