Odd–Even Effect of Repeating Aminoethylene Units in the Side Chain of N-Substituted Polyaspartamides on Gene Transfection Profiles

Citations Over TimeTop 10% of 2011 papers

Abstract

A series of the N-substituted polyaspartamides possessing repeating aminoethylene units in the side chain was prepared in this study to identify polyplexes with effective endosomal escape and low cytotoxicity. All cationic N-substituted polyaspartamides showed appreciably lower cytotoxicity than that of commercial transfection reagents. Interestingly, a distinctive odd–even effect of the repeating aminoethylene units in the polymer side chain on the efficiencies of endosomal escape and transfection to several cell lines was observed. The polyplexes from the polymers with an even number of repeating aminoethylene units (PA-Es) achieved an order of magnitude higher transfection efficiency, without marked cytotoxicity, than those of the polymers with an odd number of repeating aminoethylene units (PA-Os). This odd–even effect agreed well with the buffering capacity of these polymers as well as their capability to disrupt membrane integrity selectively at endosomal pH, leading to highly effective endosomal escape of the PA-E polyplexes. Furthermore, the formation of a polyvalent charged array with precise spacing between protonated amino groups in the polymer side chain was shown to be essential for effective disruption of the endosomal membrane, thus facilitating transport of the polyplex into the cytoplasm. These data provide useful knowledge for designing polycations to construct safe and efficient nonviral gene carriers.

Related Papers

• → High‐efficiency transfection of human endothelial cells mediated by cationic lipids(2003)4 cited
• → Enhanced transfection efficiency by using a novel semi-attachment method in cell line and primary cells(2019)2 cited
• → Determinants of protein side‐chain packing(1994)60 cited
• Study on the Method of Improving Gene Transfection Efficiency(2010)
• → ИСПОЛЬЗОВAНИЕ ПОТЕНЦИAЛA СОЦИAЛЬНЫХ ПAРТНЕРОВ В ПОДГОТОВКЕ БУДУЩИХ ПЕДAГОГОВ(2024)