Pegylated immuno-lipopolyplexes: A novel non-viral gene delivery system for liver cancer therapy
Pegylated immuno-lipopolyplexes: A novel non-viral gene delivery system for liver cancer therapy
复制标题
聚乙二醇化免疫脂多聚复合物：一种用于肝癌治疗的新型非病毒基因递送系统
DOI：
10.1016/j.jconrel.2010.02.005
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发表时间：
2010-05-21
影响因子：
10.8
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
--
作者：
Hu, Yurong;Li, Kun;Zhang, Yun
本研究利用DNA/聚乙烯亚胺构建了一种新型高效的基因传递系统--聚乙二醇化免疫脂质复合物（PILP（PEI 25 kDa）聚合复合物，以及由POPC、（DSPE）-PEG 2000和（DSPE）-PEG 2000-生物素组成的阴离子脂质体，以五种不同的脂质/DNA摩尔比（50/1、90/1、130/1、170/1和210/1），以及使用通过位于PEG间隔物远端的生物素基团缀合的链霉亲和素-单克隆抗体作为靶向抗体。该载体在保护DNA免受酶消化方面非常有效，并且即使在4 ℃下储存20天后，其颗粒大小和zeta电位也是稳定的。在脂质/DNA摩尔比为170/1时，PILP具有最高的体外转染效率，平均粒径为132 nm，平均zeta电位为+9.5 mV。这些配合物显示出高效率的基因传递到肝癌细胞，没有显着的细胞毒性。有趣的是，PILP在4 ℃下储存10天后，体外转染效率没有显著降低。PILP的静脉内给药导致报告基因EGFP和荧光素酶的肿瘤和肝脏靶向基因表达，这与用PEI/DNA复合物获得的肺靶向基因表达相反，不引起细胞因子产生和肝损伤。因此，PILP是一种很有前途的肝癌靶向基因传递系统。(C)2010爱思唯尔有限公司版权所有。
In this study, pegylated immuno-lipopolyplexes (PILP), a novel and efficient gene delivery system was developed by employing DNA/polyethylenimine (PEI 25 kDa) polyplexes, as well as anionic liposomes composed of POPC, (DSPE)-PEG2000 and (DSPE)-PEG2000-biotin, at five different lipid/DNA molar ratios (50/1, 90/1, 130/1, 170/1 and 210/1), and by using streptavidin-monoclonal antibody conjugating through the biotin group located at the distal end of the PEG spacer as targeting antibody. This vector was highly effective in protecting DNA from enzyme digestion, and stable in particle size and zeta potential even after 20 day-storage at 4 degrees C. At the lipid/DNA molar ratio 170/1, the PILP were found to have the highest in vitro transfection efficiency with an average particle size of 132 nm and an average zeta potential of +9.5 mV. These complexes showed high efficiency in gene delivery to liver cancer cells with no significant cytotoxicity. Interestingly, the in vitro transfection efficiency did not decrease significantly up to 10 days of storage of PILP at 4 degrees C. Intravenous administration of the PILP resulted in tumor and liver targeted gene expression of the reporter genes EGFP and luciferase as opposed to the lung targeted gene expression obtained with PEI/DNA complexes, causing no cytokine production and liver injury. We conclude that the PILP are promising gene delivery systems which may be used to target the liver cancer. (C) 2010 Elsevier B.V. All rights reserved.