Linear polyethylenimine-graft-chitosan copolymers as efficient DNA/siRNA delivery vectors in vitro and in vivo
Linear polyethylenimine-graft-chitosan copolymers as efficient DNA/siRNA delivery vectors in vitro and in vivo
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DOI：
10.1016/j.nano.2011.06.022
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发表时间：
2012-04-01
影响因子：
5.4
通讯作者：
Gupta, Kailash C.
中科院分区：
文献类型：
--
作者：
Tripathi, Sushil K.;Goyal, Ritu;Gupta, Kailash C.
通过与表氯醇反应，壳聚糖部分转化为其氯代醇衍生物，随后与不同量的IPEI(2.5kD)反应，得到一系列壳聚糖-IPEI(2.5kD)共聚物(CP)。然后对这些共聚物的转染效率（体外和体内）、细胞活力、DNA 释放和缓冲能力进行表征和评估。与壳聚糖、lPEI(2.5kD)、bPEI(25kD) 和 Lipofectamine 相比，CP-4 共聚物（CP 系列中最好的）在 HEK293、HeLa 和 CHO 细胞中显示出增强的转染效果（类似于 2 - 24 倍）。共聚焦显微镜显示，CP 共聚物的缓冲能力（在 3 - 7.5 的 pH 范围内）和 DNA 释放能力比壳聚糖显着增强。对小鼠静脉注射 CP-4/DNA 复合物，然后进行报告基因分析，结果显示脾脏中的基因表达最高。总的来说，这些结果证明了 CP-4 共聚物作为安全有效的非病毒载体的潜力。
Chitosan was partially converted to its chlorohydrin derivative by the reaction with epichlohydrin, which was subsequently reacted with varying amounts of lPEI(2.5kD) to obtain a series of chitosan-lPEI(2.5kD) copolymers (CP). These copolymers were then characterized and evaluated in terms of transfection efficiency (in vitro and in vivo), cell viability, DNA release and buffering capacity. The CP-4 copolymer (the best among the CP series) showed enhanced transfection (similar to 2 - 24 folds) in comparison with chitosan, lPEI(2.5kD), bPEI(25kD) and Lipofectamine in HEK293, HeLa and CHO cells. The buffering capacity (in the pH range of 3 - 7.5), as shown by confocal microscopy, and DNA-release capability of the CP copolymers, was found to be significantly enhanced over chitosan. Intravenous administration of CP-4/DNA polyplex in mice followed by the reporter gene analysis showed the highest gene expression in spleen. Collectively, these results demonstrate the potential of CP-4 copolymer as a safe and efficient nonviral vector.