Compaction and transmembrane delivery of pDNA : differences between l-PEI and two types of amphiphilic block copolymers

Titelangaben

Raup, Alexander ; Wang, Hui ; Synatschke, Christopher V. ; Jérôme, Valérie ; Agarwal, Seema ; Pergushov, Dmitry V. ; Müller, Axel H. E. ; Freitag, Ruth:
Compaction and transmembrane delivery of pDNA : differences between l-PEI and two types of amphiphilic block copolymers.
In: Biomacromolecules. Bd. 18 (2017) Heft 3 . - S. 808-818.
ISSN 1526-4602
DOI: https://doi.org/10.1021/acs.biomac.6b01678

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Abstract

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.