首页> 外文期刊>Acta biomaterialia >Alpha,beta-poly(L-aspartate-graft-PEI): A pseudo-branched PEI as a gene carrier with low toxicity and high transfection efficiency.
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Alpha,beta-poly(L-aspartate-graft-PEI): A pseudo-branched PEI as a gene carrier with low toxicity and high transfection efficiency.

机译:α,β-聚(L-天冬氨酸-移植物-PEI):伪支链PEI作为基因载体,具有低毒性和高转染效率。

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摘要

The aim of this research is to develop a novel branched polyethylenimine (PEI)-like polycation as a potential gene carrier with high gene transfection efficiency and low toxicity. In particular, alpha,beta-poly(l-aspartate-graft-PEI) (Asp-g-PEI), a pseudo-branched PEI, was synthesized by the ring-opening reaction of poly(l-succinimide) (PSI) with low molecular weight branched PEI (LMW PEI, MW=600 and 1200). Good plasmid condensation and protection ability of Asp-g-PEI were confirmed by agarose gel electrophoresis assay. Asp-g-PEI/DNA complexes showed high positive zeta potential, narrow size distribution, good dispersity and a compact spherical shape with size below 250nm when the N/P ratio was above 5, suggesting that they can be endocytosed. Cytotoxicity of Asp-g-PEI/DNA complexes was rather lower than that of PEI25K/DNA complexes, especially at high N/P ratio. The most efficient gene transfection of Asp-g-PEI/DNA complexes was similar or a little higher than that of PEI25K in 293T, HeLa and HepG2 cell lines, while almost 4 and 6 times higher than that of parent PEI1200 and PEI600, respectively, in HeLa cell line; as the molecular weight of parent PEI in Asp-g-PEI was increased from 600 to 1200, the transfection efficiency showed a tendency to decrease. The mechanism of Asp-g-PEI-mediated gene transfection was attributed to the "proton sponge effect" due to PEI in the copolymer.
机译:这项研究的目的是开发一种新型的支链聚乙烯亚胺(PEI)样聚阳离子作为具有高基因转染效率和低毒性的潜在基因载体。特别地,通过聚(1-琥珀酰亚胺)(PSI)与聚(1-琥珀酰亚胺)的开环反应合成了α,β-聚(1-天冬氨酸-接枝-PEI)(Asp-g-PEI),一种伪支链PEI。低分子量支链PEI(LMW PEI,MW = 600和1200)。琼脂糖凝胶电泳证实了Asp-g-PEI具有良好的质粒缩合和保护能力。当N / P大于5时,Asp-g-PEI / DNA复合物显示出较高的正Zeta电位,窄的粒度分布,良好的分散性和尺寸小于250nm的紧凑球形,表明它们可以被内吞。 Asp-g-PEI / DNA复合物的细胞毒性要比PEI25K / DNA复合物低,尤其是在高N / P比的情况下。在293T,HeLa和HepG2细胞系中,Asp-g-PEI / DNA复合物最有效的基因转染相似或略高于PEI25K,而分别比亲本PEI1200和PEI600高近4和6倍,在HeLa细胞系中;随着Asp-g-PEI中母体PEI的分子量从600增加到1200,转染效率呈下降趋势。 Asp-g-PEI介导的基因转染的机制归因于共聚物中的PEI引起的“质子海绵效应”。

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