Effects of charge density and hydrophobicity of poly(amido amine)s for non-viral gene delivery
Effects of charge density and hydrophobicity of poly(amido amine)s for non-viral gene delivery
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DOI：
10.1016/j.jconrel.2010.07.109
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发表时间：
2010-11-20
影响因子：
10.8
通讯作者：
Engbersen, Johan F. J.
中科院分区：
文献类型：
--
作者：
Piest, Martin;Engbersen, Johan F. J.
聚合载体中的高阳离子电荷密度导致紧密的DNA缩合，导致小的高度带正电荷的聚合复合物，其在体外显示出通常高的细胞摄取。然而，高的阳离子电荷密度也会给聚合物带来膜破坏性，从而经常导致高细胞毒性。我们先前开发了主链中具有重复二硫键的聚（酰胺基胺）（SS-PAA），其毒性显著低于PEI，这是由于这些聚合物通过二硫键的生物还原性裂解而在细胞内快速降解。在这项研究中，我们已经调查了这些聚合物的基因传递特性的电荷密度和疏水性的变化的影响，通过改变乙酰化和苯甲酰化程度的SS-PAA与氨基丁基侧链。发现疏水性苯甲酰基的引入导致更高的转染效率，在血清的存在和不存在下。(C)2010 Elsevier B. V.保留所有权利。
High cationic charge densities in polymeric vectors result in tight DNA condensation, leading to small highly positively charged polyplexes which show generally high cellular uptake in vitro. However, high cationic charge densities also introduce membrane-disruptive properties to the polymers, thereby frequently causing high cytotoxities. We previously developed poly(amido amine)s with repetitive disulfide linkages in the main chain (SS-PAAs) that are significantly less toxic than PEI, due to fast intracellular degradation of these polymers by bioreductive cleavage of the disulfide bonds. In this study we have investigated the effects of variation in charge density and hydrophobicity on the gene delivery properties of these polymers by varying the degree of acetylation and benzoylation in SS-PAAs with aminobutyl side chains. It was found that introduction of hydrophobic benzoyl groups results in higher transfection efficiencies, both in the absence and presence of serum. (C) 2010 Elsevier B.V. All rights reserved.