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.

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