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Preparation of gene drug delivery systems of cationic peptide lipid with 0G-PAMAM as hydrophilic end and its biological properties evaluation.
Chemistry and Physics of Lipids ( IF 3.4 ) Pub Date : 2018-10-09 , DOI: 10.1016/j.chemphyslip.2018.09.009
Yingying Feng 1 , Haimei Hu 1 , Shuanghong Liang 1 , Dan Wang 1
Affiliation  

As an efficient gene delivery, non-viral vectors should have high transfection efficiency, excellent endosomal escape, low cytotoxicity, and the ability to rapidly release the gene into the cytoplasm.Cationic liposome have been widely used as efficient gene carriers, but the cytotoxicity, rapid degradation and low cellular uptake are major drawback impeding its further appolication. Herein, with double lauric acid as hydrophobic chains, tartaric acid as skeleton, 0 generation PAMAM modified with lysine as hydrophilic head, a new type cationic peptide lipid was synthetised. The alkyl chain promote lipid across cell membranes and with membrane fusion, 0 generation PAMAM modified with lysine hydrophilic end amino can contain a large number of protons which can change into ammonium and combine with the DNA negatively charge phosphate groups. It is expected that this carrier has low toxicity, high transfection efficiency and targeting property. By adjusting the cationic liposome/gene weight ratio, the transfection system was optimized to improved gene transfection efficiency, reduce cytotoxicity, and increase property and stability, etc.



中文翻译:

以0G-PAMAM为亲水端的阳离子肽脂质基因递药系统的制备及其生物学性质评价。

作为一种有效的基因传递方法,非病毒载体应具有高转染效率,优异的内体逃逸性,低细胞毒性以及能够迅速将基因释放到细胞质中的能力。阳离子脂质体已被广泛用作有效的基因载体,但其细胞毒性,快速降解和低细胞摄取是阻碍其进一步应用的主要缺点。在此,以双月桂酸为疏水链,酒石酸为骨架,以赖氨酸为亲水头修饰的0代PAMAM,合成了新型阳离子肽脂质。烷基链促进脂质跨细胞膜扩散,并通过膜融合作用,用赖氨酸亲水末端氨基修饰的0代PAMAM可以包含大量质子,这些质子可以变成铵并与带负电荷的DNA磷酸基团结合。预期该载体具有低毒性,高转染效率和靶向性质。通过调节阳离子脂质体/基因的重量比,优化了转染系统,以提高基因转染效率,降低细胞毒性,提高性能和稳定性等。

更新日期:2018-10-09
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