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

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Tytuł:: Eradication of cancer stem cells in triple negative breast cancer using doxorubicin/pluronic polymeric micelles.
Autorzy:: Zhao Y; 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.
Alakhova DY; 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.
Zhao X; Department of Genetics, Cell Biology and Anatomy, College of Medicine, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE, USA.
Band V; 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.
Batrakova EV; 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.
Kabanov AV; 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: .
Źródło:: Nanomedicine : nanotechnology, biology, and medicine [Nanomedicine] 2020 Feb; Vol. 24, pp. 102124. Date of Electronic Publication: 2019 Nov 20.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
Język:: English
Imprint Name(s):: Original Publication: New York, NY : Elsevier, c2005-
MeSH Terms:: Micelles*
Neoplastic Stem Cells*/metabolism
Neoplastic Stem Cells*/pathology
Triple Negative Breast Neoplasms*/drug therapy
Triple Negative Breast Neoplasms*/metabolism
Triple Negative Breast Neoplasms*/pathology
Doxorubicin/*analogs & derivatives
Drug Resistance, Neoplasm/*drug effects
Poloxamer/*analogs & derivatives
Animals ; Doxorubicin/chemistry ; Doxorubicin/pharmacology ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mice ; Mice, Nude ; Neoplasm Proteins/biosynthesis ; Poloxamer/chemistry ; Poloxamer/pharmacology ; Xenograft Model Antitumor Assays
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Grant Information:: R01 CA089225 United States CA NCI NIH HHS; R01 CA144027 United States CA NCI NIH HHS; R01 CA184088 United States CA NCI NIH HHS; U54 CA151652 United States CA NCI NIH HHS
Contributed Indexing:: Keywords: Cancer; Cancer stem cells; Doxorubicin; Drug resistance; Pluronic; Poloxamer; Triple negative breast cancer
Substance Nomenclature:: 0 (Micelles)
0 (Neoplasm Proteins)
0 (SP 1049C)
106392-12-5 (Poloxamer)
80168379AG (Doxorubicin)
Entry Date(s):: Date Created: 20191123 Date Completed: 20201112 Latest Revision: 20220716
Update Code:: 20240105
PubMed Central ID:: PMC9038110
DOI:: 10.1016/j.nano.2019.102124
PMID:: 31756533
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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.
(Copyright © 2019. Published by Elsevier Inc.)

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