|516. Raup, A.; Wang, H.; Synatschke, C.V.; Jérôme, V.; Agarwal, S.; Pergushov, D.V.; Müller, A.H.E.; Freitag, R.: Compaction and transmembrane delivery of pDNA: differences between l-PEI and two types of amphiphilicblock copolymers, Biomacromolecules accepted (2017)|
Polycations are popular agents for non-viral delivery of DNA to mammalian cells. Adding hydrophobic, biodegradable, or cell penetrating functions could help to improve their performance, which at present is below that of viral agents. A crucial first step in gene delivery is the complexation of the DNA. The characteristics of these ‘polyplexes’ presumably influence or even determine the subsequent steps of membrane passage, intracellular travelling / DNA release, and nuclear up-take. Herein, polyplexes formed with linear poly(ethylenimine) (l-PEI) are compared to complexes generated with functionalized diblock copolymers. While l-PEI interacts only electrostatically with the DNA, interaction in case of the diblock polymers may be mixed- mode. In certain cases transfection efficiency improved when the polyplexes were formed in hypertonic solution. Moreover, whereas conventional PEI-based polyplexes enter the cells via endocytosis, at least one of the diblock agents seemed to promote entry via transient destabilization of the plasma membrane.