Multifunctional polymer vesicles for cancer stem cells-targeted drug/siRNA therapy

Abstract

Cancer stem cells (CSCs) are responsible for origin, growth, recurrence, and metastasis of tumor, and are closely linked to the failure of chemotherapy due to their self-renewal and multilineage differentiation capability with an innate resistance to cytotoxic agents. We have recently reported a novel EpCAM (epithelial cell adhesion molecule)-monoclonal-antibody-labeled CSCs-targeting, noncytotoxic and pH-sensitive block copolymer vesicle as a nanocarrier of anticancer drug and siRNA (to overcome CSCs drug resistance by silencing the expression of oncogenes). This vesicle shows high delivery efficacy of both doxorubicin hydrochloride (DOX·HCl) and siRNA to the CSCs. Furthermore, the DOX or siRNA loaded CSCs-targeting vesicles exhibited much better CSCs killing and tumor growth inhibition capabilities with much lower toxicity to normal cells (IC 50,DOX decreased by 80%) compared with non-CSCs-targeting vesicles. Overall, these vesicles have significant implications for overcoming CSCs chemo-resistance in cancer chemotherapy.