Targeted Gene Delivery Mediated by Folate-polyethylenimine-block-poly(ethylene glycol) with Receptor Selectivity
Targeted Gene Delivery Mediated by Folate-polyethylenimine-block-poly(ethylene glycol) with Receptor Selectivity
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DOI：
10.1021/bc8004057
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发表时间：
2009-03-01
影响因子：
4.7
通讯作者：
Zhuo, Ren-Xi
中科院分区：
文献类型：
--
作者：
Cheng, Han;Zhu, Jing-Ling;Zhuo, Ren-Xi
叶酸受体(FR)是一种在大量癌细胞中过度表达的肿瘤标志物。叶酸对FR有很高的亲和力，并通过其伽玛-羧基衍生化后保持其结合亲和力。因此，本文设计了叶酸-聚乙烯亚胺-嵌段-聚乙二醇膜(FOL-PEI-b-PEG)，用于特异性受体靶向的基因传递。通过琼脂糖凝胶电泳法、颗粒大小和Zeta电位法对所得的FOL-PEI-b-PEG/DNA络合物进行了物理化学表征。结果表明，FOL-PEI-b-PEG能紧密凝聚DNA，并具有合适的粒径。细胞毒性研究表明，与25 kDa PEI相比，共聚物的毒性较小。荧光素酶活性测定和绿色荧光蛋白(GFP)检测也证实FOL-PEI-b-PEG是一种有效的基因载体。重要的是，含有游离叶酸的FOL-PEI-b-PEG对FR阳性的HeLa细胞的转染率明显低于不含游离叶酸的共聚物，提示FOL-PEI-b-PEG作为靶向基因载体具有很大的潜力。
The folate receptor (FR) is a tumor marker overexpressed in large numbers of cancer cells. Folic acid has high affinity to the FR and retains its binding affinity upon derivatization via its gamma-carboxyl. Therefore, in this article, folate-polyethylenimine-block-poly(ethylene glycol) (FOL-PEI-b-PEG) was designed for specific receptor targeted gene delivery. Physicochemical characterizations of resulting FOL-PEI-b-PEG/DNA complexes in terms of agarose gel electrophoresis, particle size, and zeta potential measurements were investigated. The results indicated that FOL-PEI-b-PEG was able to condense plasmid DNA tightly with a suitable particle size. The cytotoxicity study indicated that the copolymer exhibited less toxicity in comparison with that of 25 kDa PEI. Luciferase assay and green fluorescent protein (GFP) detections were also used to confirm that FOL-PEI-b-PEG could be an effective gene vector. Importantly, transfection efficiency of FOL-PEI-b-PEG with free folic acid was much lower than that of the copolymer without free folic acid on FR-positive HeLa cells, suggesting that FOL-PEI-b-PEG has great potential as a targeting gene vector.