Different Effects of Reversible Electroporation-Mediated Fe3O4@AuNPs Delivery as Radiosensitizing Agents on Cancer Cells versus Normal Cells

Aim: In the present study, we sought to enhance the efficacy of radiotherapy via increasing the cellular uptake of Fe 3 O 4 @AuNPs as radiosensitizing agents using reversible electroporation, attaining a higher sensitivity for cancer cells to therapy-induced damage. Methods: The KB human nasopharyngeal carcinoma cell line was treated with different concentrations of gold-coated magnetic nanoparticles. The cells then received electroporation (750[Formula: see text]V/cm, 8 pulses for a duration 100[Formula: see text][Formula: see text]s with 100[Formula: see text]ms intervals) and radiotherapy (6MV X-ray, 2[Formula: see text]Gy). Control groups were carefully considered to assess the pure effect of both single and combinational therapeutic protocols. The MTT test and flow cytometry assay using Annexin V-PI kit were performed to evaluate potential effects on cell survival rate and to determine the induced level of apoptosis. Additionally, cellular uptake of nanoparticles was assessed and quantified using ICP-OES analysis. Results: Our study showed that nanoparticles and the applied procedure of electroporation had no considerable effects when utilized separately, but their combined application induced significant cell death ([Formula: see text]45%) and apoptosis ([Formula: see text]17%). Besides, the application of Fe 3 O 4 @AuNPs in the presence of electric field, 24[Formula: see text]h before the radiotherapy of tumor cells enhanced the cancer cell death ([Formula: see text]53%) as well as apoptosis rate ([Formula: see text]33%). The same scenario was also observed with normal HGF human gingival fibroblasts, confirmed by significantly lower levels of cell death and apoptosis. Conclusion: It can be concluded that electric fields at low voltage levels may significantly and selectively enhance the entry of nanoparticles into cancer cells, thereby accentuating the sensitivity of these cells to nanoparticle-mediated radiation therapy.