The role and mechanisms of zinc oxide nanoparticles in the improvement of the radiosensitivity of lung cancer cells in clinically relevant megavoltage radiation energies in-vitro

Objective(s): Semiconductor zinc oxide nanoparticles (ZnO NPs) have unique properties, such as inherent selectivity and photosensitization effects under ultraviolet (UV) radiation. ZnO NPs serve as promising anticancer agents. However, UV radiation limits their penetration into the body. In most clinical settings, it is essential to use high-energy photons in the treatment of deep-seated tumors. The present study aimed to evaluate the radiosensitization effects of ZnO NPs on human lung cancer cells under megavoltage (MV) X-ray irradiation. Materials and Methods: ZnO NPs with the mean diameter of seven nanometers were synthesized and characterized. The cytotoxicity and cellular uptake of ZnO NPs were evaluated in SKLC-6 lung cancer and MRC-5 normal lung cells using the 3-(4,5-dimethylthiazol-yl)-5(3-carboxymethoxyphenyl)-2H-tetrazolium (MTT) and inductively coupled plasma-mass spectrometry assays, respectively. In addition, the radiosensitization effects of ZnO NPs were investigated under MV irradiation using a clonogenic survival assay. Apoptosis induction and DNA damage were also evaluated using flow cytometry and cytokinesis-block micronucleus assay, respectively.Results: ZnO NPs were taken up and reduced the viability of the cancer cells at a higher rate compared to the normal cells. Moreover, ZnO NPs significantly enhanced the radiosensitivity of the cancer cells with the sensitizer enhancement ratios of 1.23 and 1.31 at the concentrations of 10 and 20 μg/ml, respectively. However, they had no significant effect on the radiosensitivity of the normal cells. Apoptosis induction and DNA damage also improved at a higher rate in the cancer cells compared to the normal cells with the combination of ZnO NPs with MV radiation.Conclusion: According to the results, ZnO NPs had the potential to be a selective radiosensitizer for lung cancer radiotherapy under MV X-ray irradiation. Some of the cytotoxic and genotoxic mechanisms in radiosensitization by ZnO NPs were elevated apoptosis induction and DNA damage levels.