Tumor stem cells have emerged as the new targets for anti-
cancer therapy, besides
tumor cells themselves. To eradicate both
breast cancer cells and
breast cancer stem cells which can not be eliminated by the conventional
chemotherapy,
octreotide (Oct)-modified
paclitaxel (PTX)-loaded
PEG-b-PCL polymeric
micelles (Oct-M-PTX) and
salinomycin (SAL)-loaded
PEG-b-PCL polymeric
micelles (M-SAL) were developed and investigated in combination. In this study, Oct that targets
somatostatin receptors (SSTR) overexpressed in
tumors including
breast cancer, was coupled to the PEG end of
PEG-b-PCL, and all the
micelles were prepared using thin film hydration method. Results showed that the particle size of all the
micelles was approximately 25-30 nm, and the encapsulation efficiency was >90%. Quantitative and qualitative analysis demonstrated that Oct facilitates the uptake of
micelles in SSTR overexpressed
breast cancer MCF-7 cells while free Oct inhibited cellular uptake of Oct-modified
micelles, revealing the mechanism of receptor-mediated endocytosis.
Breast cancer stem cells (side population cells, SP cells) were sorted from MCF-7 cells and identified with the CD44+/CD24- phenotype. M-SAL was capable of decreasing the proportion of SP cells, and its suppression was more potent in SP cells than that in
cancer cells. As compared to PTX-loaded
micelles (M-PTX), the inhibition of Oct-M-PTX against MCF-7 cells was stronger while such effect significantly increased when applying Oct-M-PTX in combination with M-SAL. In the MCF-7 xenografts, the combination
therapy with Oct-M-PTX plus M-SAL produced the strongest antitumor efficacy, in accord with the combination treatment in vitro. Compared with free SAL, M-SAL was found to be more effective in suppressing
breast cancer stem cells in vivo. Thus, this combination
therapy may provide a strategy to improve treatment of breast
cancers for eradication of
breast cancer cells together with
breast cancer stem cells.