Poly(ethylenimine) conjugated bioreducible dendrimer for efficient gene delivery.
Poly(ethylenimine) conjugated bioreducible dendrimer for efficient gene delivery.
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DOI：
10.1016/j.jconrel.2015.11.005
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发表时间：
2015-12-28
期刊：
影响因子：
--
通讯作者：
Kim SW
中科院分区：
文献类型：
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作者：
Nam K;Jung S;Nam JP;Kim SW
支化聚亚胺（PEI） 25 kDa是一种高效的基因传递载体，具有出色的基因凝聚能力和较大的核内体逃逸活性。然而，它也会引起更高的细胞毒性。PEI的转染效率和毒性高度依赖于它们的分子量和结构。我们开发了一种生物可还原的聚亚胺（PEI (-s-s-)），源自低分子量PEI (1.8 kDa)，用于高效的基因传递。生物可还原的核心分子有望增加分子量并降低共聚物的细胞毒性。与支链PEI 25kda、Lipofectamine®2000和FuGENE®6相比，PEI （-s-s-）多聚体显示出更高的转染效率和更低的细胞毒性。此外，PEI （-s-s-）衍生物（16 kDa）形成了稳定的多聚物，zeta电位值为+34 mV，多聚物尺寸为61 nm。PEI （-s-s-）衍生物（16 kDa）转染效率高：在HeLa细胞中是支化PEI （25 kDa）的3.6倍，在H9C2细胞中是Lipofectamine®2000的7.4倍。与Lipofectamine®2000和PEI 25kda相比，这些衍生物在各种细胞类型中也显示出更低的细胞毒性。此外，新合成的PEI （-s-s-）衍生物具有较高的重现性。
Branched poly(ethylenimine) (PEI) 25 kDa is an efficient gene delivery vector with outstanding gene condensation ability and great endosome escape activity. However, it also induces higher cytotoxicity. Transfection efficiency and toxicity of PEI are highly dependent upon their molecular weight and structure. We developed a bioreducible poly(ethylenimine) (PEI (-s-s-)) derived from low molecular weight PEI (1.8 kDa) for efficient gene delivery. Bioreducible core molecule is expected to increase molecular weight and reduce the cytotoxicity of the copolymer. PEI (-s-s-) polyplexes showed higher transfection efficiency and lower cytotoxicity compared to branched PEI 25 kDa, Lipofectamine® 2000 and, FuGENE® 6. In addition, PEI (-s-s-) derivative (16 kDa) formed stable polyplexes with a zeta-potential value of +34 mV and polyplex size of 61 nm. PEI (-s-s-) derivative (16 kDa) showed excellent transfection efficiency: 3.6 times higher than branched PEI 25 kDa in HeLa cells and 7.4 times higher than Lipofectamine® 2000 in H9C2 cell. The derivatives also showed lower cytotoxicity compared with Lipofectamine® 2000 and PEI 25 kDa in various cell types. In addition, newly synthesized PEI (-s-s-) derivatives have high reproducibility.