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

Authors Lara-Cruz C, Jiménez-Salazar JE, Arteaga M, Arredondo M, Ramón-Gallegos E, Batina N, Damián-Matsumura P

Received 1 December 2018

Accepted for publication 6 March 2019

Published 1 May 2019 Volume 2019:14 Pages 2705—2718

DOI https://doi.org/10.2147/IJN.S196683

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 4

Editor who approved publication: Dr Thomas J Webster


Carlos Lara-Cruz,1 Javier E Jiménez-Salazar,2 Marcela Arteaga,2 Michelle Arredondo,1 Eva Ramón-Gallegos,3 Nikola Batina,1 Pablo Damián-Matsumura2

1Nanotechnology 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, Mexico

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.

Keywords: nanotherapy, hormone therapy, estrogen-induced vesicle formation, AuNP cellular uptake, membrane roughness, endocytosis


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