ABSTRACT
AIM: The combination of phototherapy and chemotherapy (chemophototherapy), presents a promising multimodal method for comprehensive cancer treatment. The aim of this study is to investigate the influence of low doses of zinc oxide (ZnO) nanofluids and ultraviolet A (UVA) irradiation on the cytotoxicity and cellular uptake of doxorubicin (DOX) on human prostate cancer DU145 cells. MATERIALS AND METHODS: ZnO nanoparticles were prepared by the solvothermal method and 10% bovine serum albumin was used as the dispersant. The cytotoxic effect of DOX alone and in combination with different concentrations of ZnO nanofluids (0.95-15.6 µg/ml) in the presence and absence of UVA irradiation on DU145 cells was evaluated by -(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. DOX residue inside and outside of DU145 cells was explored by fluorescence microscopy and UV-Vis absorption spectroscopy, respectively. The role of ZnO nanofluids and UVA irradiation in DOX-induced apoptosis and cell cycle arrest were evaluated by DAPI staining, comet assay, and flow cytometry. RESULTS: The results revealed that low dose of ZnO nanofluids (0.95 µg/ml) accompanied with irradiation enhanced the cytotoxicity and intracellular delivery of DOX in DU145 cells. The percentage of chromatin fragmentation/condensation and DNA tail of DU145 cells treated simultaneously with DOX and ZnO nanofluids was increased after UVA irradiation, whereas no significant changes in cell cycle progression were observed. CONCLUSION: The results indicate that ZnO nanofluids in the presence of UVA irradiation could increase DOX efficiency in DU145 cells, suggesting such modality combinations as a promising approach in cancer treatment.