The improvement of anti-proliferation activity against breast cancer cell line of thioguanine by gold nanoparticles

Abstract

Drug resistance and damage to non-malignant normal cells are the big medical challenges in cancer chemotherapy. As a currently in use anticancer drug, several side effects have been attributed to 6-Thioguanine (6TG). There are several options to help in minimizing or preventing the unwanted harmful effects of a drug. Loading of 6TG on the surface of gold nanoparticles (GNPs) which have unique physicochemical properties for transporting and unloading pharmaceuticals seems one of the useful strategies to overcome the deleterious effects of this anticancer drug. In the current study, GNPs with almost spherical morphology and the average diameter between 4 and 6 nm which is larger than the cutoff size of the renal system were used for functionalization with 6TG. In order to characterize shape and size of GNPs, as well as the percent entrapment efficiency of 6TG, transmission electron microscopy, UV/Vis spectroscopy, and thermal gravimetric analysis were applied. To estimate the improvement of the drug delivery of GNPs, breast cancer cells were treated with 6TG and 6TG-functionalized GNPs (6TG-GNPs), and cell viability was studied in vitro, by 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay. As shown, both free 6TG and 6TG-GNP revealed anti-proliferation activity against the cancer cells in time- and dose-dependent manners. Moreover, 6TG-GNP displays significantly greater anti-proliferation activity than that of free 6TG in all incubation times and at the concentration of 12.5 μM and above. Overall, the improvement of anti-proliferation activity of 6TG-GNPs compared to that of 6TG can be attributed to enhanced intracellular uptake of the functionalized GNPs via the mechanism of endocytosis. Moreover, this study may suggest GNP as a useful carrier of 6TG against its several adverse effects in cancer therapy.