Fiche publication
Date publication
février 2016
Journal
Biomacromolecules
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHAN-SENG Delphine
Tous les auteurs :
Ghobadi AF, Letteri R, Parelkar SS, Zhao Y, Chan-Seng D, Emrick T, Jayaraman A
Lien Pubmed
Résumé
Polymer-based gene delivery vehicles benefit from the presence of hydrophilic groups that mitigate the inherent toxicity of polycations and that provide tunable polymer-DNA binding strength and stable complexes (polyplexes). However, hydrophilic groups screen charge, and as such can reduce cell uptake and transfection efficiency. We report the effect of embedding zwitterionic sulfobetaine (SB) groups in cationic comb polymers, using a combination of experiments and molecular simulations. Ring-opening metathesis polymerization (ROMP) produced comb polymers with tetralysine (K4) and SB pendent groups. Dynamic light scattering, zeta potential measurements, and fluorescence-based experiments, together with coarse-grained molecular dynamics simulations, described the effect of SB groups on the size, shape, surface charge, composition, and DNA binding strength of polyplexes formed using these comb polymers. Experiments and simulations showed that increasing SB composition in the comb polymers decreased polymer-DNA binding strength, while simulations indicated that the SB groups distributed throughout the polyplex. This allows polyplexes to maintain a positive surface charge and provide high levels of gene expression in live cells. Notably, comb polymers with nearly 50 mol % SB form polyplexes that exhibit positive surface charge similarly as polyplexes formed from purely cationic comb polymers, indicating the ability to introduce an appreciable amount of SB functionality without screening surface charge. This integrated simulation-experimental study demonstrates the effectiveness of incorporating zwitterions in polyplexes, while guiding the design of new and effective gene delivery vectors.
Mots clés
Cell Line, Tumor, Cyclooctanes, chemistry, DNA, chemistry, Genetic Therapy, Humans, Molecular Dynamics Simulation, Polymers, chemistry, Transfection
Référence
Biomacromolecules. 2016 02 8;17(2):546-57
