AI Article Synopsis
- High cationic charge densities in polymeric vectors lead to compact DNA complexes, improving cellular uptake but also increasing cytotoxicity due to membrane disruption.
- We developed less toxic poly(amido amine)s (SS-PAAs) that degrade quickly inside cells due to disulfide linkages, making them safer than traditional polymers like PEI.
- Modifying SS-PAAs with hydrophobic benzoyl groups enhanced gene delivery efficiency, even when serum is present, by adjusting charge density and hydrophobicity.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.jconrel.2010.07.109 | DOI Listing |
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