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Versatile reticular polyethylenimine derivative-mediated targeted drug and gene codelivery for tumor therapy.
- Source :
-
Molecular pharmaceutics [Mol Pharm] 2014 Oct 06; Vol. 11 (10), pp. 3307-21. Date of Electronic Publication: 2014 Aug 01. - Publication Year :
- 2014
-
Abstract
- The study is aimed to develop a versatile reticular polyethylenimine (PEI) derivative eprosartan-g-PEI (ESP) conjugate-mediated targeted drug and gene codelivery system for tumor therapy. Eprosartan (ES), an angiotensin II type 1 receptor blocker (ARB), which has been proven to exert beneficial effects on tumor progression, vascularization, and metastasis as the conventional antihypertensive drug, was conjugated with PEI-1.8K chains into ESP via a bis-amide bond of pH-sensitivity to overcome high cytotoxicity and nontargeted gene delivery of PEI-25K. P53 gene was encapsulated in the ESP to form the codelivery system of ESP/p53 complexes, and this system was comprehensively characterized. In vitro ESP/p53 complexes had a significant effect on inhibiting angiogenesis by reducing the expression and secretion of VEGF. In vivo the effective antitumor activity of ESP/p53 complexes was observed on nude mice bearing PANC-1 xenografts, and the microvessel density (MVD) examination demonstrated that ESP/p53 complex-produced antitumor efficacy was closely correlated with the efficient angiogenesis repression. These findings disclosed that the multifunctional ESP/p53 complexes might be a promising dual anticancer drug and gene codelivery system.
- Subjects :
- Acrylates chemistry
Acrylates therapeutic use
Animals
Antineoplastic Agents therapeutic use
Cell Line, Tumor
Enzyme-Linked Immunosorbent Assay
Humans
Imidazoles chemistry
Imidazoles therapeutic use
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Microscopy, Atomic Force
Microvessels drug effects
Neovascularization, Pathologic drug therapy
Neovascularization, Pathologic metabolism
Thiophenes chemistry
Thiophenes therapeutic use
Antineoplastic Agents chemistry
Drug Delivery Systems methods
Polyethyleneimine chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1543-8392
- Volume :
- 11
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Molecular pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 25058017
- Full Text :
- https://doi.org/10.1021/mp5001263