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

Abstract

Carlos Lara-Cruz,1 Javier E Jiménez-Salazar,2 Marcela Arteaga,2 Michelle Arredondo,1 Eva Ramón-Gallegos,3 Nikola Batina,1 Pablo Damián-Matsumura21Nanotechnology and Molecular Engineering Laboratory, Department of Chemistry, Division of Basic Science and Engineering (DCBI), Universidad Autónoma Metropolitana (UAM), Mexico City, Mexico; 2Department of Biology of Reproduction, Division of Biological Sciences and Health (DCBS), Universidad Autónoma Metropolitana (UAM), Mexico City, Mexico; 3Department of Morphology, National School of Biological Sciences, Instituto Politécnico Nacional, Mexico City, MexicoPurpose: 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.Keywords: nanotherapy, hormone therapy, estrogen-induced vesicle formation, AuNP cellular uptake, membrane roughness, endocytosis

Keywords

• Nanotherapy
• hormone therapy
• estrogen-induced vesicle formation
• AuNP cellular uptake
• membrane roughness
• endocytosis