The eradication of breast cancer cells and stem cells by 8-hydroxyquinoline-loaded hyaluronan modified mesoporous silica nanoparticle-supported lipid bilayers containing docetaxel

Abstract

Breast cancer stem cells (BCSCs), which can fully recapitulate the tumor origin and are often resistant to chemotherapy and radiotherapy, are currently considered as a major obstacle for breast cancer treatment. To achieve the goal of both targeting BCSCs and bulk breast cancer cells, we developed 8-hydroxyquinoline-loaded hyaluronan modified mesoporous silica nanoparticles (MSN)-supported lipid bilayers (HA-MSS) and docetaxel-loaded MSS. The results showed that the size of all the nanoparticles was smaller than 200 nm. BCSCs were enriched from MCF-7 cells by a sphere formation method and identified with the CD44(+)/CD24(-) phenotype. Quantitative and qualitative analysis demonstrated that HA promotes the uptake of HA-MSS in CD44-overexpressing MCF-7 mammospheres, revealing the mechanism of receptor-mediated endocytosis. DTX or DTX-loaded MSS showed much enhanced cytotoxicity against MCF-7 cells compared with MCF-7 mammospheres, whereas 8-HQ or 8-HQ-loaded HA-MSS showed much enhanced cytotoxicity against MCF-7 mammospheres compared with MCF-7 cells. In the MCF-7 xenografts in mice, the combination therapy with DTX-loaded MSS plus 8-HQ-loaded HA-MSS produced the strongest antitumor efficacy, with little systemic toxicity (reflecting by loss of body weight) in mice. Thus, this combination therapy may provide a potential strategy to improve the therapy of breast cancer by eradication of breast cancer cells together with BCSCs.

Keywords: 8-HQ; 8-Hydroxyquinoline (8-HQ); 8-hydroxyquinoline; BCSCs; Breast cancer stem cells; CSCs; DTX; Docetaxel (DTX); EDC; HA; HA-MSS; Hyaluronan (HA); MSN; MSS; Mesoporous silica nanoparticle; NPs; PEG; SLB; Supported lipid bilayer; breast cancer stem cells; cancer stem cells; docetaxel; ethyl-dimethyl-aminopropyl-carbodiimide; hyaluronan modified mesoporous silica nanoparticle-supported lipid bilayers; hyaluronan or hyaluronic acid; mesoporous silica nanoparticle; mesoporous silica nanoparticle-supported lipid bilayers; nanoparticles; polyethylene glycol; supported lipid bilayers.