title: Versatile reticular polyethylenimine derivative-mediated targeted drug and gene codelivery for tumor therapy.
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.
authors: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University , 24 Tongjiaxiang, Nanjing 210009, China.
authors: Xuefang
authors: X
authors: Ding
authors: Wei
authors: W
authors: Wang
authors: Yazhe
authors: Y
authors: Wang
authors: Xiuli
authors: X
authors: Bao
authors: Yu
authors: Y
authors: Wang
authors: Cheng
authors: C
authors: Wang
authors: Jian
authors: J
authors: Chen
authors: Fangrong
authors: F
authors: Zhang
authors: Jianping
authors: J
authors: Zhou
mesh_terms: D000179:Acrylates / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018625:Microscopy, Atomic Force; D055806:Microvessels / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry*; D013876:Thiophenes / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000179:Acrylates; D000970:Antineoplastic Agents; D007093:Imidazoles; D013876:Thiophenes; C068373:eprosartan; D011094:Polyethyleneimine
keywords: angiotensin II type-1 receptor; codelivery; eprosartan; p53; polyethylenimine; tumor therapy