Efficient siRNA delivery using a polyamidoamine dendrimer with a modified pentaerythritol core.
Efficient siRNA delivery using a polyamidoamine dendrimer with a modified pentaerythritol core.
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DOI：
10.1007/s11095-012-0676-x
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发表时间：
2012-06
影响因子：
3.7
通讯作者：
Lee, Robert J.
中科院分区：
文献类型：
--
作者：
Zhang, Yue;Zhou, Chenguang;Kwak, Kwang Joo;Wang, Xinmei;Yung, Bryant;Lee, L. James;Wang, Yanming;Wang, Peng George;Lee, Robert J.
将siRNA输送到细胞中仍然是一个关键的挑战。我们的实验室已经展示了一种新型的聚氨基胺（PAMAM）树状大分子，其修饰的季戊四醇衍生物核心（PD树状大分子）具有高质粒DNA转染效率和低细胞毒性。在这里，我们评估PD树状大分子作为siRNA载体。琼脂糖凝胶电泳和原子力显微镜证实了第5代(G5)-PD树突/siRNA纳米颗粒（NPs）的形成。使用G5 PD树突/抗荧光素酶siRNA NPs转染具有稳定荧光素酶表达的SK Hep-1细胞。我们还研究了各种内吞途径抑制剂对SK Hep-1细胞中G5 PD树突状分子/siRNA NPs摄取的影响。琼脂糖凝胶电泳结果表明，G5 PD树状大分子与siRNA形成了分子量比为bb0 0.5:1的NPs。G5 PD树突状分子在重量比为3.0:1及以上时表现出有效的荧光素酶基因沉默。用胞吞抑制剂处理表明，网格蛋白介导的胞吞作用是G5-PD树突/siRNA NPs进入细胞的主要胞吞途径。这些结果表明，新型G5 PD树突状物具有较高的siRNA递送活性，有望作为一种治疗应用的递送剂。
Delivery of siRNA into cells remains a critical challenge. Our lab has shown a novel polyamidoamine (PAMAM) dendrimer with modified pentaerythritol derivative core (PD dendrimer) to exhibit high plasmid DNA transfection efficiency and low cytotoxicity. Here, we evaluate PD dendrimer as a siRNA carrier. Agarose gel electrophoresis and AFM were used to confirm formation of generation 5 (G5)-PD dendrimer/siRNA nanoparticles (NPs). G5 PD dendrimer/anti-luciferase siRNA NPs were used to transfect SK Hep-1 cells with stable luciferase expression. Effects of various endocytic pathway inhibitors on uptake of G5 PD dendrimer/siRNA NPs in SK Hep-1 cells were also investigated. Agarose gel electrophoresis indicated that G5 PD dendrimer and siRNA formed NPs at weight ratios >0.5:1. G5 PD dendrimer showed effective luciferase gene silencing when weight ratio was 3.0:1 and above. Treatment with endocytosis inhibitors showed that clathrin-mediated endocytosis was the main endocytic pathway by which G5-PD dendrimer/siRNA NPs enter the cell. These results show that the novel G5 PD dendrimer has high siRNA delivery activity and is promising as a delivery agent for its therapeutic application.
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DOI：
10.1083/jcb.200302028
发表时间：
2003-05-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nabi IR;Le PU
通讯作者：
Le PU
DOI：
10.1007/s10856-007-3193-4
发表时间：
2008-02-01
影响因子：
3.7
作者：
Huang, Yongzhuo;Chen, Jinliang;Liang, Wenquan
通讯作者：
Liang, Wenquan
影响因子：
5.8
作者：
Kim, Hyun-Ki;Davaa, Enkhzaya;Park, Jeong-Sook
通讯作者：
Park, Jeong-Sook
影响因子：
5.8
作者：
Zhou, Chenguang;Yu, Bo;Yang, Xiaojuan;Huo, Tianyao;Lee, L. James;Barth, Rolf F.;Lee, Robert J.
通讯作者：
Lee, Robert J.
影响因子：
46.9
作者：
Tyagi, S;Kramer, FR
通讯作者：
Kramer, FR