title: Liposomes, modified with PTD(HIV-1) peptide, containing epirubicin and celecoxib, to target vasculogenic mimicry channels in invasive breast cancer.
abstract: Refractoriness of invasive breast cancer is closely related with the vasculogenic mimicry (VM) channels, which exhibit highly drug resistance to conventional chemotherapies. In the present study, the nanostructured targeting epirubicin plus celecoxib liposomes were developed by modifying a human immunodeficiency virus peptide lipid-derivative conjugate (DSPE-PEG2000-PTDHIV-1) for elimination of invasive breast cancer cells along with their VM channels. The studies were undertaken on invasive human breast cancer MDA-MB-435S cells and MDA-MB-435S xenografts in nude mice. The constructed targeting epirubicin plus celecoxib liposomes were approximately 100 nm in size. In vitro results showed that the targeting liposomes exhibited strong transport ability across cell and nuclei membranes of invasive breast cancer, were able to penetrate and destruct the invasive breast cancer spheroids, initiated apoptosis via activating apoptotic enzymes (caspase 8, 3), and destroyed the VM channels via down-regulating the protein indicators (MMP-9, VE-Cad, FAK, EphA2 and HIF-1α) in invasive breast cancer cells. In vivo results demonstrated that the targeting liposomes displayed a prolonged circulation time in blood system, accumulated more in tumor location, were able to eliminate the VM channels and angiogenesis in tumor tissues, and resulted in a robust overall anticancer efficacy in invasive breast cancer MDA-MB-435S xenografts in nude mice. In conclusion, the nanostructured targeting epirubicin plus celecoxib liposomes could eliminate invasive breast cancer along with the VM channels, hence providing a promising strategy for treatment of invasive breast cancer.
authors.affiliation: 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: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xue-Tao
authors.initials: XT
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Meng-Ge
authors.initials: MG
authors.lastname: Sun
authors.affiliation: 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: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: 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: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Cheng-Xiang
authors.initials: CX
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: luwl@bjmu.edu.cn.
authors.forename: Wan-Liang
authors.initials: WL
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001940:Breast / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D000068579:Celecoxib; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D015251:Epirubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D015497:HIV-1 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000970:Antineoplastic Agents; D008081:Liposomes; D010455:Peptides; D010714:Phosphatidylethanolamines; D011720:Pyrazoles; D013449:Sulfonamides; D011092:Polyethylene Glycols; D015251:Epirubicin; D000068579:Celecoxib
keywords: Anticancer efficacy; Invasive breast cancer; PTD(HIV-1) peptide; Targeting epirubicin plus celecoxib liposomes; Vasculogenic mimicry channels