Simultaneous Targeting of Differentiated Breast Cancer Cells and Breast Cancer Stem Cells by Combination of Docetaxel- and Sulforaphane-Loaded Self-Assembled Poly(D, L-lactide-co-glycolide)/Hyaluronic Acid Block Copolymer-Based Nanoparticles.

Abstract

Breast cancer stem cells (BCSCs) are implicated in the initiation and progression of breast cancer and are responsible for metastasis and recurrence. In this study, we attempted to simultaneously target differentiated breast cancer cells (DBCCs) and BCSCs by using a combination of docetaxel (DTX)- and sulforaphane (SFN)-loaded poly(D, L-lactide-coglycolide)/hyaluronic acid (PLGA-b-HA)-based nanoparticles. BCSCs were identified as having an ESA+CD44+CD24– phenotype, which exhibited docetaxel resistance. Drug-loaded nanoparticles exhibited enhanced cytotoxicity towards both DBCCs and BCSCs compared with free drugs. SFN-loaded nanoparticles were more effective in inhibiting BCSCs than free SFN in vitro by down-regulating β-catenin expression. In vivo analysis of anti-tumor activity showed that the combination therapy with DTX- and SFN-loaded nanoparticles had the strongest antitumor efficacy. In vivo analysis of anti-BCSCs activity showed that the self-renewal ability of BCSCs was strongly inhibited in DTX- and SFN-loaded nanoparticle-treated groups. In conclusion, the combination of SFN- and DTX-loaded PLGA-b-HA nanoparticles shows therapeutic potential in the treatment of breast cancer by simultaneously targeting DBCCs and BCSCs.