Polyethylene glycol-grafted poly-L-lysine as polymeric gene carrier

Polyethylene glycol-grafted poly-L-lysine as polymeric gene carrier
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DOI:
10.1016/s0168-3659(97)00174-0
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发表时间:
1998-06-01
影响因子:
10.8
通讯作者:
Kim, SW
Kim, SW
中科院分区:
医学1区
文献类型:
--
作者:
Choi, YH;Liu, F;Kim, SW

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本文报道了一种新型的基因载体--聚乙二醇(PEG)接枝的多聚赖氨酸(PLL,mol.重量= 25 000),分别以5、10和25mol%(即PEG分别修饰了PLL的5、10和25%的ε-氨基)的摩尔比对PLL进行接枝改性。这些新的基因载体,命名为梳形PEG-g-PLL共聚物,显示了5- 30倍的转染效率增加相比,PLL单独对人癌细胞系。结果表明,质粒DNA/PEG-g-PLL复合物通过内吞作用转染Hep G2细胞,氯喹可提高转染效率。尽管阳离子脂质制剂Lipofectin(TM)在Hep G2细胞中显示出比PEG-g-PLL略高的转染效率,但我们设计的PEG-g-PLL表现出较低的细胞毒性、早期基因表达和长达96小时的基因表达维持。(C)1998年Elsevier Science B.V.
A new series of gene carriers, polyethylene glycol (PEG)-grafted poly-L-lysine (PLL, mol. wt.=25 000) with three different PEG-grafted ratios (5, 10 and 25 mole%, which means 5, 10 and 25% of epsilon-amino group of PLL was modified by PEG), was synthesized. These new gene carriers, named comb-shaped PEG-g-PLL copolymer, showed a 5- to 30-fold increase in transfection efficiency compared to PLL alone on a human carcinoma cell line. It is likely that Hep G2 cells were transfected by plasmid DNA/PEG-g-PLL complexes through an endocytosis mechanism due to the fact that chloroquine increased transfection efficiency. Although Lipofectin(TM), a cationic lipid formulation, showed slightly higher transfection efficiency than PEG-g-PLL in Hep G2 cells, our designed PEG-g-PLL demonstrated lower cytotoxicity, early gene expression and maintenance of gene expression for up to 96 h. (C) 1998 Elsevier Science B.V.