Versatile Reticular Polyethylenimine Derivative-Mediated Targeted Drug and Gene Codelivery for Tumor Therapy
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- 作者：Xuefang Ding ; Wei Wang ; Yazhe Wang ; Xiuli Bao ; Yu Wang ; Cheng Wang ; Jian Chen ; Fangrong Zhang ; Jianping Zhou
- 刊名：Molecular Pharmaceutics
- 出版年：2014
- 出版时间：October 6, 2014
- 年：2014
- 卷：11
- 期：10
- 页码：3307-3321
- 全文大小：841K
- ISSN：1543-8392
文摘
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.