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

Abstract

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

Targeting the organelle for radiosensitization in cancer radiotherapy

“…Moreover, their effectiveness is still limited by the accumulation in tumor tissue and the poor effect of inducing TME, such as ROS. Therefore, there is an urgent need to further enhance their RT effect by precisely controlling the size and shape of nanoparticles or modifying their surface [ 40 , 58 , 61 ]. However, the preparation methods for these sensitizers are generally complicated, and their versatility is limited.…”

Understanding the molecular mechanism responsible for developing therapeutic radiation-induced radioresistance of rectal cancer and improving the clinical outcomes of radiotherapy - A review

“… 100 According to research, Fe3O4@Cus-PEG NPs are a promising nano radio-sensitizing agent, and the presence of nanoparticles enhanced the effects of X-ray radiation. 101 …”

The effect of nanoparticle coating on biological, chemical and biophysical parameters influencing radiosensitization in nanoparticle-aided radiation therapy

“…Radiosensitization of breast cancer to mega-voltage radiation therapy with PEG-coated gold-iron nanoparticles was increased under MV beams of 18 MV [ 84 ]. Mohammadian et al [ 85 ] suggested PEG-coated iron nanoparticles as promising nano-radiosensitizer in colorectal cancer treatment under 6-MV X-ray photons. Geng et al [ 11 ] demonstrated that glucose-coated gold NPs achieved superior enhancement ratios at 90 kVp than 6 MV.…”