Synthesis and characterization of folate-PEG-grafted-hyperbranched-PEI for tumor-targeted gene delivery
Synthesis and characterization of folate-PEG-grafted-hyperbranched-PEI for tumor-targeted gene delivery
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用于肿瘤靶向基因递送的叶酸-PEG-接枝超支化-PEI 的合成和表征
DOI：
10.1016/j.bbrc.2008.01.024
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发表时间：
2008-03-21
影响因子：
3.1
通讯作者：
Peng, Ying
中科院分区：
文献类型：
--
作者：
Liang, Bing;He, Ming-Liang;Peng, Ying
开发高效、低毒的基因传递系统是基因治疗面临的一个巨大挑战。非病毒载体仍然是有吸引力的，尽管目前的试剂显示出一些缺点（即，转染效率低，毒性大）。为了克服聚乙烯亚胺（PEI）的高毒性和聚乙二醇化PEI（PEG-PEI）的低转染效率，我们将细胞特异性靶分子叶酸（FA）连接到聚乙二醇（PEG）上，然后将FA-PEG接枝到超支化PEI 25 kDa上。在合适的N/P比下，FA-PEG-grafted-hyperbubricated-PEI（FA-PEG-PEI）可有效地将质粒DNA（pDNA）凝聚成表面带正电荷的纳米粒子。在不同的细胞系中测试（即，HEK 293 T、神经胶质瘤C6和肝癌HepG 2细胞），将FA-PEG-PEI添加到PEG-PEI中没有显著的细胞毒性。更重要的是，在FA靶向细胞中表现出显著的转染效率。报告基因分析表明FA-PEG-PEI/pDNA复合物在叶酸受体（FR）阳性（HEK 293 T和C6）细胞中具有显著高于PEI/pDNA的转基因活性，而在FR阴性（HepG 2）细胞中没有。这些结果表明FA-PEG-PEI具有良好的生物相容性、潜在的生物降解性和较高的基因转染效率，是一种很有前途的基因载体。(c)2008年爱思唯尔公司All rights reserved.
A great challenge for gene therapy is to develop a high efficient gene delivery system with low toxicity. Nonviral vectors are still attractive although the current agents' displayed some disadvantages (i.e., low transfection efficiency, high toxicity). To overcome the high toxicity of poly(ethylene imine) (PEI) and low transfection efficiency of PEGylated PEI (PEG-PEI), we linked a cell specific target molecule folate (FA) on poly(ethylene glycol) (PEG) and then grafted the FA-PEG onto hyperbranched PEI 25 kDa. The FA-PEG- grafted-hyperbranched-PEI (FA-PEG-PEI) effectively condensed plasmid DNA (pDNA) into nanoparticles with positive surface charge under a suitable N/P ratio. Tested in deferent cell lines (i.e., HEK 293T, glioma C6 and hepatoma HepG2 cells), no significant cytotoxicity of FA-PEG-PEI was added to PEG-PEI. More importantly, significant transfection efficiency was exhibited in FA-targeted cells. Reporter assay showed that FA-PEG-PEI/pDNA complexes had significantly higher transgene activity than that of PEI/pDNA in folate-receptor (FR) positive (HEK 293T and C6) cells but not FR-negative (HepG2) cells. These results indicated that FA-PEG-PEI might be a promising candidate for gene delivery with the characteristics of good biocompatibility, potential biodegradability, and relatively high gene transfection efficiency. (c) 2008 Elsevier Inc. All rights reserved.