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Life Sci. 2019 Jun 6:116545. doi: 10.1016/j.lfs.2019.116545. [Epub ahead of print]

Enhanced penetration and cytotoxicity of metformin and collagenase conjugated gold nanoparticles in breast cancer spheroids.

Author information

1
Department of Medical Biotechnology, Zanjan University of Medical Sciences, Zanjan, Iran; Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
2
Department of Medical Nanotechnology, Zanjan University of Medical Sciences, Zanjan, Iran. Electronic address: nadri_s@zums.ac.ir.
3
Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
4
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
5
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
6
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: yomidi@tbzmed.ac.ir.

Abstract

AIMS:

The extracellular matrix (ECM) within the tumor nest plays a key role in cancer cell proliferation and invasion. It has been proven that the increased density of ECM, especially collagen network, correlates with the poor distribution of gold-nanoparticles (GNPs) to the tumor mass. Here, for the first time, we examined the combined effect of collagenase (COL) with metformin (MET)-conjugated GNPs on mammosphere generated from JIMT-1 breast cell line in vitro.

MAIN METHODS:

Mammospheres (on days 7 and 14) and monolayer culture were treated with MET, MET-GNPs, and a mixture of COL-GNPs and MET-GNPs for 5 days. To assess the impacts of the engineered NPs on the survival/apoptosis of cancer cells and cancer stem cells (CSCs), the amount/activity of collagen and the expression of pyruvate kinase M2, different analyses were applied, including MTT, flow cytometry, immunofluorescence, ELISA and real-time PCR analyses. Our results confirmed the enhanced cytotoxic effects of MET-GNPs combined with COL-GNPs on mammospheres compared to the cells treated with MET alone or MET-GNPs.

KEY FINDINGS:

Upon treatment with the mixture of MET-GNPs and COL-GNPs, the apoptotic cells were significantly increased. A significant reduction was found in the number of CD24-/CD44+ CSCs and the amount of collagen in the group received a mixture of MET-GNPs and COL-GNPs.

SIGNIFICANCE:

Based on our findings, the use of COL can improve the cellular interaction/penetration of MET-GNPs in mammospheres and its antitumor impacts on the CSCs.

KEYWORDS:

Cancer stem cells; Collagenase; Gold nanoparticles; Mammospheres; Metformin; Nanomedicine

PMID:
31176782
DOI:
10.1016/j.lfs.2019.116545

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