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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.