Department of Biomedical Chemistry, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
Department of Biomedical Chemistry, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
J Control Release. 2010 Nov 20;148(1):83-90. doi: 10.1016/j.jconrel.2010.07.109. Epub 2010 Jul 24.
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.
高分子载体中高正电荷密度会导致 DNA 紧密凝聚，形成带高度正电荷的小多聚物，通常在体外具有较高的细胞摄取率。然而，高正电荷密度也会使聚合物具有膜破坏特性，从而经常导致高细胞毒性。我们之前开发了具有重复二硫键连接的主链的聚（酰胺-胺）（SS-PAAs），由于这些聚合物通过二硫键的生物还原断裂在细胞内快速降解，因此其毒性明显低于 PEI。在这项研究中，我们通过改变具有氨基丁基侧链的 SS-PAAs 的乙酰化和苯甲酰化程度，研究了电荷密度和疏水性的变化对这些聚合物基因传递特性的影响。结果发现，引入疏水性苯甲酰基会导致转染效率提高，无论是在无血清还是有血清的情况下。
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