Inhibiting Notch Activity in Breast Cancer Stem Cells by Glucose Functionalized
Nanoparticles Carrying ?-secretase Inhibitors
#MMPMID26916284
Mamaeva V
; Niemi R
; Beck M
; Özliseli E
; Desai D
; Landor S
; Gronroos T
; Kronqvist P
; Pettersen IK
; McCormack E
; Rosenholm JM
; Linden M
; Sahlgren C
Mol Ther
2016[May]; 24
(5
): 926-36
PMID26916284
show ga
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 ?-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.
|Amyloid Precursor Protein Secretases/antagonists & inhibitors
[MESH]
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