ZnO nanofluids for the improved cytotoxicity and cellular uptake of doxorubicin

Objective(s): Combination anticancer therapy holds promise for improving the therapeutic efficacy of chemotherapy drugs such as doxorubicin (DOX) as well as decreasing their dose-limiting side effects. Overcoming the side effects of doxorubicin (DOX) is a major challenge to the effective treatment of cancer. Zinc oxide nanoparticles (ZnO NPs) are emerging as potent tools for a wide variety of biomedical applications. The aim of this study was to develop a combinatorial approach for enhancing the anticancer efficacy and cellular uptake of DOX. Materials and Methods: ZnO NPs were synthesized by the solvothermal method and were characterized by X-ray diffraction (XRD), dynamic light scattering (DLS) and transmission electron microscopy (TEM). ZnO NPs were dispersed in 10% bovine serum albumin (BSA) and the cytotoxic effect of the resulting ZnO nanofluids was evaluated alone and in combination with DOX on DU145 cells. The influence of ZnO nanofluids on the cellular uptake of DOX and DOX-induced catalase mRNA expression were investigated by fluorescence microscopy and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively. Results: The MTT results revealed that ZnO nanofluids decreased the cell viability of DU145 cells in a timeand dose-dependent manner. Simultaneous combination treatment of DOX and ZnO nanofluid showed a significant increase in anticancer activity and the cellular uptake of DOX compared to DOX alone. Also, a time-dependent reduction of catalase mRNA expression was observed in the cells treated with ZnO nanofluids and DOX, alone and in combination with each other. Conclusion: These results indicate the role of ZnO nanofluid as a growth-inhibitory agent and a drug delivery system for DOX in DU145 cells. Thus, ZnO nanofluid could be a candidate for combination chemotherapy.