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具有改良季戊四醇核心的聚酰胺-胺树枝状聚合物作为基因载体,具有高效和低细胞毒性。

Polyamidoamine dendrimers with a modified Pentaerythritol core having high efficiency and low cytotoxicity as gene carriers.

机构信息

Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, China.

出版信息

Biomacromolecules. 2009 Mar 9;10(3):617-22. doi: 10.1021/bm801333s.

Abstract

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.

摘要

聚酰胺-胺(PAMAM)树枝状聚合物是最有效的聚合物基因载体之一。本研究描述了一类新型 PAMAM 树枝状聚合物,它可以使用戊四醇衍生物(PD)作为核心来合成,该核心具有 12 个支链。这种在合成发散树枝状聚合物方面的新方法可以快速增加支链的数量,从而更容易获得具有高代和足够大的分子尺寸的树枝状聚合物。本研究中合成的第 3-5 代 PD 树枝状聚合物能够有效地将 DNA 浓缩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了它们的转染效率。结果表明,与商业非病毒基因载体聚乙烯亚胺(PEI)、聚赖氨酸(PLL)和以乙二胺为核心的 PAMAM 树枝状聚合物(第 5 代和第 7 代)相比,这些 PD 树枝状聚合物具有更高的转染效率,但细胞毒性却低得多。这些结果表明,PD 树枝状聚合物具有高转染效率和低细胞毒性,有望成为新型非病毒基因载体。

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