Soft Nanocontainers Based on Hydroxyethylated Geminis: Role of Spacer in Self-Assembling, Solubilization, and Complexation with Oligonucleotide

Abstract

Copyright © 2020 American Chemical Society. Self-organization of hydroxyethylated gemini surfactants with different spacer fragments 16-s-16(OH) (s = 4, 6, 10, and 12) was studied in single solutions and in binary surfactant-oligonucleotide systems. Despite the fact that aggregation activity and solubilization capacity of aggregates decrease with an increase in spacer length, gemini with the longer spacer demonstrate superior binding capacity toward oligonucleotide as compared to single head surfactant and gemini analogs with shorter spacers. The detailed study testified that gemini with longer spacers are characterized by a looser packing mode, a moist and more polar interior, and tend to show polymorphism. These features in combination with favorable geometry factor providing suitable orientation of components are probably responsible for the beneficial lipoplex formation in the case of longer spacers. The effectiveness of oligonucleotide-surfactant complexation changes in the same order as transfection efficacy mediated by these gemini reported earlier [Zakharova, L. et al. Colloids Surf. B, 2016, 140, 269-277], which indicates that physicochemical aspects probably play a key role upon the design of nonviral vectors and may be used for prediction of transfection efficacy mediated by amphiphilic agents.