Gold nanoparticle uptake is enhanced by estradiol in MCF-7 breast cancer cells

Purpose: In the present study, we investigated the effects of 17β-estradiol (E₂) on membrane roughness and gold nanoparticle (AuNP) uptake in MCF-7 breast cancer cells. Methods: Estrogen receptor (ER)-positive breast cancer cells (MCF-7) were exposed to bare 20 nm AuNPs in the presence and absence of 1×10^-9 M E₂ for different time intervals for up to 24 hrs. The effects of AuNP incorporation and E₂ incubation on the MCF-7 cell surface roughness were measured using atomic force microscopy (AFM). Endocytic vesicle formation was studied using confocal laser scanning microscopy (CLSM). Finally, the results were confirmed by hyperspectral optical microscopy. Results: High-resolution AFM images of the surfaces of MCF-7 membranes (up to 250 nm²) were obtained. The incubation of cells for 12 hrs with AuNP and E₂ increased the cell membrane roughness by 95% and 30% compared with the groups treated with vehicle (ethanol) or AuNPs only, respectively. This effect was blocked by an ER antagonist (7α,17β-[9-[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol [ICI] 182,780). Higher amounts of AuNPs were localized inside MCF-7 cells around the nucleus, even after 6 hrs of E₂ incubation, compared with vehicle-treated cells. Endolysosome formation was induced by E₂, which may be associated with an increase in AuNP-uptake. Conclusions: E₂ enhances AuNP incorporation in MCF-7 cells by modulating of plasma membrane roughness and inducing lysosomal endocytosis. These findings provide new insights into combined nanotherapies and hormone therapies for breast cancer.