Polyamidoamine Dendrimers with a Modified Pentaerythritol Core Having High Efficiency and Low Cytotoxicity as Gene Carriers
Polyamidoamine Dendrimers with a Modified Pentaerythritol Core Having High Efficiency and Low Cytotoxicity as Gene Carriers
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具有修饰季戊四醇核心的聚酰胺胺树枝状聚合物作为基因载体具有高效率和低细胞毒性
DOI：
10.1021/bm801333s
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发表时间：
2009-03-01
影响因子：
6.2
通讯作者：
Yu, Yaoting
中科院分区：
文献类型：
--
作者：
Wang, Yanming;Kong, Weiling;Yu, Yaoting
聚酰胺-胺（PAMAM）树枝状大分子代表了最有效的聚合物基因载体之一。本研究描述了一个新的家庭的PAMAM树枝状聚合物，可以合成使用Pentaelide衍生物（PD）作为核心，拥有12个分支。这种新的方法在合成发散的树枝状大分子提供了一个快速增加的分支的数量，这使得它更容易获得高代和足够大的分子尺寸的树枝状大分子。本研究中合成的第3-5代PD树枝状聚合物可以有效地将DNA凝聚成带有轻微正电荷的纳米级复合物。在不同的细胞系中评估它们的转染效率。发现这些PD树枝状聚合物显示出比商业非病毒基因载体聚乙烯亚胺（PEI）、聚赖氨酸（PLL）和具有乙二胺核心的PAMAM树枝状聚合物（第5代和第7代）更高的转染效率，但细胞毒性低得多。结果表明，具有高转染效率和低细胞毒性，PD树枝状聚合物有望成为新型的非病毒基因载体。
Polyamidoamine (PAMAM) dendrimers represent one of the most efficient polymeric gene carriers. This study describes a new family of PAMAM dendrimers that can be synthesized using a Pentaerythritol derivative (PD) as a core that possesses 12 branches. This new approach in the synthesis of divergent dendrimers provided a rapid increase in the number of branches, which made it easier to obtain dendrimers with high generation and large enough molecular size. The PD dendrimers of generations 3-5 synthesized in this study could efficiently condense DNA into nanoscale complexes with slightly positive charges. Their transfection efficiency was evaluated in different cell lines. These PD dendrimers were found to show higher transfection efficiency, but much lower cytotoxicity, than the commercial nonviral gene carriers polyethyleneimine (PEI), polylysine (PLL), and PAMAM dendrimers with an ethylenediamine core (generations 5 and 7). The results indicate that, with high transfection efficiency and low cytotoxicity, the PD dendrimers hold promise as novel nonviral gene carriers.