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Liposomes, modified with PTD(HIV-1) peptide, containing epirubicin and celecoxib, to target vasculogenic mimicry channels in invasive breast cancer.
- Source :
-
Biomaterials [Biomaterials] 2014 Aug; Vol. 35 (26), pp. 7610-21. Date of Electronic Publication: 2014 Jun 07. - Publication Year :
- 2014
-
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.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents therapeutic use
Apoptosis drug effects
Breast blood supply
Breast drug effects
Breast pathology
Breast Neoplasms blood supply
Breast Neoplasms pathology
Celecoxib
Cell Line, Tumor
Drug Delivery Systems
Epirubicin therapeutic use
Female
HIV-1 metabolism
Humans
Liposomes metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness pathology
Neoplasm Invasiveness prevention & control
Neovascularization, Pathologic drug therapy
Neovascularization, Pathologic pathology
Peptides metabolism
Phosphatidylethanolamines chemistry
Phosphatidylethanolamines metabolism
Polyethylene Glycols chemistry
Polyethylene Glycols metabolism
Pyrazoles therapeutic use
Sulfonamides therapeutic use
Antineoplastic Agents administration & dosage
Breast Neoplasms drug therapy
Epirubicin administration & dosage
HIV-1 chemistry
Liposomes chemistry
Peptides chemistry
Pyrazoles administration & dosage
Sulfonamides administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5905
- Volume :
- 35
- Issue :
- 26
- Database :
- MEDLINE
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 24912818
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2014.05.040