A1 Refereed original research article in a scientific journal
Inhibiting Notch Activity in Breast Cancer Stem Cells by Glucose Functionalized Nanoparticles Carrying gamma-secretase Inhibitors
Authors: Mamaeva V, Niemi R, Beck M, Ozliseli E, Desai D, Landor S, Gronroos T, Kronqvist P, Pettersen IKN, McCormack E, Rosenholm JM, Linden M, Sahlgren C
Publisher: NATURE PUBLISHING GROUP
Publication year: 2016
Journal: Molecular Therapy
Journal name in source: MOLECULAR THERAPY
Journal acronym: MOL THER
Volume: 24
Issue: 5
First page : 926
Last page: 936
Number of pages: 11
ISSN: 1525-0016
eISSN: 1525-0024
DOI: https://doi.org/10.1038/mt.2016.42
Self-archived copy’s web address: https://research.utu.fi/converis/portal/Publication/17026891
Cancer stem cells (CSCs) are a challenge in cancer treatment due to their therapy resistance. We demonstrated that enhanced Notch signaling in breast cancer promotes self-renewal of CSCs that display high glycolytic activity and aggressive hormone-independent tumor growth in vivo. We took advantage of the glycolytic phenotype and the dependence on Notch activity of the CSCs and designed nanoparticles to target the CSCs. Mesoporous silica nanoparticles were functionalized with glucose moieties and loaded with a gamma-secretase inhibitor, a potent interceptor of Notch signaling. Cancer cells and CSCs in vitro and in vivo efficiently internalized these particles, and particle uptake correlated with the glycolytic profile of the cells. Nanoparticle treatment of breast cancer transplants on chick embryo chorioallantoic membranes efficiently reduced the cancer stem cell population of the tumor. Our data reveal that specific CSC characteristics can be utilized in nanoparticle design to improve CSC-targeted drug delivery and therapy.
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