Improve the cytotoxic effects of megavoltage radiation treatment by Fe₃O₄@Cus–PEG nanoparticles as a novel radiosensitizer in colorectal cancer cells

Background: To enhance the performance of radiotherapy, emerging nanoparticles that can professionally enhance X-ray irradiation to destruct cancer cells are extremely necessary. Here, we examined the potential of PEG-coated magnetite copper sulfide hetero-nanoparticles (Fe₃O₄@Cus–PEG) as a radiosensitizer agent. Methods: Fe₃O₄@Cus–PEG nanoparticles were synthesized and characterized. The toxicity of nanoparticles on HT-29 colorectal cancer cells was assessed by the MTT assay. The radio-sensitizing effects of Fe₃O₄@Cus–PEG nanoparticles on HT-29 cancer cells were investigated by the MTT and colony formation assays. Moreover, the underlying mechanisms for Fe₃O₄@Cus–PEG nanoparticles to improve the radiation sensitivity of cells were evaluated. Results: The results demonstrated that nanoparticles enhanced the effects of X-ray irradiation in a dose-dependent manner. The effects of combined treatments (nanoparticles and X-ray radiation) were strongly synergistic. The sensitizing enhancement ratio (SER) of nanoparticles was 2.02. Our in vitro assays demonstrated that the nitric oxide production, the intracellular hydrogen peroxide concentration, and the expression level of Bax and Caspase-3 genes significantly increased in the cells treated with the combination of nanoparticles and radiation. Whereas, the Glutathione peroxidase enzyme activity and the expression level of the Bcl-2 gene in the combined treatment significantly decreased compared to the radiation alone. Conclusions: Our study suggests that Fe₃O₄@Cus–PEG nanoparticles are the promising nano radio-sensitizing agents for the treatment of cancer cells to enhance the efficacy of radiation therapy through increasing the reactive oxygen species generation, nitric oxide production, and inducing apoptosis. Graphical Abstract: [Figure not available: see fulltext.].