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

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.
AuthorsYi Zhao, Daria Y Alakhova, Xiangshan Zhao, Vimla Band, Elena V Batrakova, Alexander V Kabanov
JournalNanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 24 Pg. 102124 (02 2020) ISSN: 1549-9642 [Electronic] United States
PMID31756533 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
CopyrightCopyright © 2019. Published by Elsevier Inc.
Chemical References
  • Micelles
  • Neoplasm Proteins
  • SP 1049C
  • Poloxamer
  • Doxorubicin
Topics
  • Animals
  • Doxorubicin (analogs & derivatives, chemistry, 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, pathology)
  • Poloxamer (analogs & derivatives, chemistry, pharmacology)
  • Triple Negative Breast Neoplasms (drug therapy, metabolism, pathology)
  • Xenograft Model Antitumor Assays

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