title: 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.
authors.affiliation: Department of Pharmaceutical Science, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Jingbin
authors.initials: J
authors.lastname: Huang
authors.forename: Xinxia
authors.initials: X
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yu
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Junjie
authors.initials: J
authors.lastname: Liu
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Sun
authors.forename: Hao
authors.initials: H
authors.lastname: Zou
authors.forename: Duxin
authors.initials: D
authors.lastname: Sun
authors.forename: Guichen
authors.initials: G
authors.lastname: Zhou
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.forename: Yanqiang
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006912:Hydroxyquinolines / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D061986:MCF-7 Cells; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*; D043823:Taxoids / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D006912:Hydroxyquinolines; D008051:Lipid Bilayers; D043823:Taxoids; D000077143:Docetaxel; D012822:Silicon Dioxide; D006820:Hyaluronic Acid
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