Eradication of cancer stem cells in triple negative breast cancer using doxorubicin/pluronic polymeric micelles

Yi Zhao; Daria Y Alakhova; Xiangshan Zhao; Vimla Band; Elena V Batrakova; Alexander V Kabanov

doi:10.1016/j.nano.2019.102124

Eradication of cancer stem cells in triple negative breast cancer using doxorubicin/pluronic polymeric micelles

Nanomedicine. 2020 Feb:24:102124. doi: 10.1016/j.nano.2019.102124. Epub 2019 Nov 20.

Authors

Yi Zhao¹, Daria Y Alakhova¹, Xiangshan Zhao², Vimla Band³, Elena V Batrakova¹, Alexander V Kabanov⁴

Affiliations

¹ Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC, USA.
² Department of Genetics, Cell Biology and Anatomy, College of Medicine, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE, USA.
³ Department of Genetics, Cell Biology and Anatomy, College of Medicine, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE, USA; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
⁴ Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC, USA; Laboratory of Chemical Design of Bionanomaterials, Faculty of Chemistry, M.V. Lomonosov Moscow State University, Moscow, Russia. Electronic address: kabanov@unc.edu.

Abstract

The potency of polymeric micelle-based doxorubicin, SP1049C, against cancer stem cells (CSCs) in triple negative breast cancer (TNBC) is evaluated. CSCs with high epithelial specific antigen (ESA), high CD44 and low CD24 expression levels were derived from the TNBC cancer cells, MDA-MB-231 and MDA-MB-468. These CSCs were resistant to free doxorubicin (Dox) and displayed increased colony formation, migration, and invasion in vitro, along with higher tumorigenicity in vivo, compared to the parental and non-CSCs counterparts. SP1049C downregulated the expression and inhibited the functional activity of the breast cancer resistance protein (BCRP/ABCG2) in CSCs. The polymeric micelle drug had higher cytotoxicity and potency in reducing the colony formation of CSCs compared to the free drug. It was also more potent in inhibiting the tumor growth in the orthotopic animal tumor models derived from CSCs. These results indicate that SP1049C is active against CSCs and has potential in treating TNBC.

Keywords: Cancer; Cancer stem cells; Doxorubicin; Drug resistance; Pluronic; Poloxamer; Triple negative breast cancer.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Doxorubicin / analogs & derivatives*
Doxorubicin / chemistry
Doxorubicin / pharmacology
Drug Resistance, Neoplasm / drug effects*
Female
Gene Expression Regulation, Neoplastic / drug effects
Humans
Mice
Mice, Nude
Micelles*
Neoplasm Proteins / biosynthesis
Neoplastic Stem Cells* / metabolism
Neoplastic Stem Cells* / pathology
Poloxamer / analogs & derivatives*
Poloxamer / chemistry
Poloxamer / pharmacology
Triple Negative Breast Neoplasms* / drug therapy
Triple Negative Breast Neoplasms* / metabolism
Triple Negative Breast Neoplasms* / pathology
Xenograft Model Antitumor Assays

Substances

Micelles
Neoplasm Proteins
SP 1049C
Poloxamer
Doxorubicin

Abstract

Publication types

MeSH terms

Substances

Grants and funding