title: Application of functional vincristine plus dasatinib liposomes to deletion of vasculogenic mimicry channels in triple-negative breast cancer.
abstract: Standard chemotherapy cannot eradicate triple-negative breast cancer (TNBC) while the residual cancer cells readily form the vasculogenic mimicry (VM) channels, which lead to the relapse of cancer after treatment. In this study, the functional vincristine plus dasatinib liposomes, modified by a targeting molecule DSPE-PEG2000-c(RGDyK), were fabricated to address this issue. The investigations were performed on TNBC MDA-MB-231 cells and MDA-MB-231 xenografts in nude mice. The liposomes exhibited the superior performances in the following aspects: the enhancement of cellular uptake via targeted action; the induction of apoptosis via activation of caspase 8, 9, and 3, increased expression of Bax, decreased expression of Mcl-1, and generation of reactive oxygen species (ROS); and the deletion of VM channels via inhibitions on the VM channel indicators, which consisted of vascular endothelial-cadherin (VE-Cad), focal adhesion kinase (FAK), phosphatidylinositide 3-kinase (PI3K), and matrix metallopeptidases (MMP-2, and MMP-9). Furthermore, the liposomes displayed the prolonged circulation time in the blood, the increased accumulation in tumor tissue, and the improved therapeutic efficacy along with deletion of VM channels in the TNBC-bearing mice. In conclusion, the nanostructured functional drug-loaded liposomes may provide a promising strategy for the treatment of invasive TNBC along with deletion of VM channels.
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zeng
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Rui-Jun
authors.initials: RJ
authors.lastname: Ju
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Xie
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Mu
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Hu
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Jia-Shuan
authors.initials: JS
authors.lastname: Wu
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Wan-Liang
authors.initials: WL
authors.lastname: Lu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D000069439:Dasatinib / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011897:Random Allocation; D064726:Triple Negative Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D014750:Vincristine / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; D014750:Vincristine; D000069439:Dasatinib
keywords: dasatinib; functional liposome; triple-negative breast cancer; vasculogenic mimicry channel; vincristine