Gold Nanoparticle Uptake Is Enhanced By Estradiol In Mcf-7 Breast Cancer Cells

INTERNATIONAL JOURNAL OF NANOMEDICINE(2019)

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Abstract
Purpose: In the present study, we investigated the effects of 17 beta-estradiol (E-2) 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 1x10(-9) M E-2 for different time intervals for up to 24 hrs. The effects of AuNP incorporation and E-2 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 nm(2)) were obtained. The incubation of cells for 12 hrs with AuNP and E-2 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 (7 alpha,17 beta-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 E-2 incubation, compared with vehicle-treated cells. Endolysosome formation was induced by E-2, which may be associated with an increase in AuNP-uptake.Conclusions: E-2 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.
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Key words
nanotherapy,hormone therapy,estrogen-induced vesicle formation,AuNP cellular uptake,membrane roughness,endocytosis
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