DNA polyplexes based on degradable oligoethylenimine-derivatives: Combination with EGF receptor targeting and endosomal release functions

被引:33
作者
Kloeckner, Julia
Boeckle, Sabine
Persson, Daniel
Roedl, Wolfgang
Ogris, Manfred
Berg, Kristian
Wagner, Ernst
机构
[1] Univ Munich, Dept Pharm, D-81377 Munich, Germany
[2] Norwegian Radium Hosp, Dept Radiat Biol, Inst Canc Res, N-0310 Oslo, Norway
关键词
endosomal release; epidermal growth factor; melittin; nonviral vectors; oligoethylenimine; photochemical internalization; polyplex;
D O I
10.1016/j.jconrel.2006.07.002
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Combination of the degradable polymeric gene carriers OEI-HD-1 and LT-OEI-HD-1 with an EGF targeting conjugate resulted in strongly (up to 900-fold) enhanced polyplex activity in EGF-receptor rich HUH7 hepatocellular carcinoma cells. The targeting ligand effect was DNA dose dependent, could be blocked by competitive receptor binding with unbound EGF ligand, and was not observed in receptor-negative control cells. Measures which enhance intracellular endosomal escape, either photochemically enhanced intracellular release (PCI) or the incorporation of a novel membrane-active melittin analog NMA-3, further enhanced gene transfer activity of EGF/OEI-HD-1 polyplexes. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:115 / 122
页数:8
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