Investigating the synergistic effects of gold nanoparticles and electroporation in sensitization of human intestinal colon cancer HT-29 cells to 6MV photon beam

Abstract

Introduction: Radiation therapy (RT) is the gold standard treatment for more than half of known tumors. There is increasing evidence that combining radiation therapy with a radiosensitizer can enhance the efficiency of this treatment modality. A radiosensitizer preferably enhances dose at the site of tumor and increases discrimination between tumor and normal surrounding tissues. Gold nanoparticles (GNPs) and electroporation (EP) have shown good potential as radiosensitizers. Therefore, the present study assessed the sensitizing effects of EP, GNPs, and combined EP-GNPs on the dose enhancement factor(DEF) for 6 MV photon energy. Materials and Methods: In this in-vitro study, intestinal colon cancer (HT-29) cells treated with four different protocols: ionizing radiation alone (IR, control group), EP+IR, GNPs+IR and GNPs+EP+IR. Radiosensitization was assessed by colony formation assay at 6 MV photon energy. The survival curve was estimated using MATLAB software and DEF for each combination treatment group was calculated by dividing of LD50 (50% lethal dose) of control group with combination treatment group. Results: when the cells were treated with EP prior to IR the DEF of 1.36 was achieved. Treatment of cells with GNPs immediately before irradiation resulted in DEF of 1.17. In this group, GNPs did not significantly enhance the effect of IR due to having not enough time for GNPs to enter and accumulate in the target cells. However, when EP was added to the protocol of GNPs+IR group, DEF of 2.61 was observed. The observed difference between DEF values of GNPs+IR and GNPs+EP+IR groups can be attributed to the act of EP as a GNPs delivery system in GNPs+EP+IR group. Conclusion: Combined GNPs-EP protocol could induce synergistic effects in HT-29 cells and it can be beneficially used for the treatment of intrinsically less radiosensitive tumors.