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Efficient and non-toxic gene delivery by anionic lipoplexes based on polyprenyl ammonium salts and their effects on cell physiology

Rak, Monika and Ochałek, A and Bielecka, Ewa and Latasiewicz, Joanna and Gawarecka, Katarzyna and Sroka, Joanna and Czyz, Jaroslaw and Piwowarczyk, Katarzyna and Masnyk, Marek and Chmielewski, Marek and Chojnacki, Tadeusz and Swiezewska, Ewa and Madeja, Zbigniew (2016) Efficient and non-toxic gene delivery by anionic lipoplexes based on polyprenyl ammonium salts and their effects on cell physiology. Journal of Gene Medicine, 18 (11-12). pp. 331-342.


Official URL: http://onlinelibrary.wiley.com/doi/10.1002/jgm.293...


Background One of the major challenges limiting development of gene therapy is absence of efficient and safe gene carriers. Among the non-viral gene delivery methods, lipofection is considered as one of the most promising. In this study a set of cationic polyprenyl derivatives (trimethylpolyprenylammonium iodides – PTAI) with different lengths of polyprenyl chains (from 7, 8 and 11 to 15 isoprene units) was suggested as a component of efficient DNA vehicles. Methods Optimization studies were conducted for PTAI in combination with co-lipid DOPE (dioleoylphosphatidylethanolamine) on DU145 human prostate cancer cells using: size and zeta potential measurements, confocal microscopy, fluorescein diacetate/ethidium bromide test, cell counting, time-lapse monitoring of cell movement, gap junctional intracellular coupling analysis, antimicrobial activity assay, red blood cell hemolysis test. Results The results show that the lipofecting activity of PTAI allows effective transfection of plasmid DNA complexes in negatively charged lipoplexes of 200 - 500 nm size into cells without significant side effects on cell physiology (viability, proliferation, morphology, migration and gap junctional intercellular coupling – GJIC). Moreover, PTAI-based vehicles exhibit a potent bactericidal activity against Staphylococcus aureus and Escherichia coli. The developed anionic lipoplexes are safe towards human red blood cell membranes which are not disrupted in their presence. Conclusions The developed carriers constitute a group of promising lipofecting agents of a new type and can be utilized as effective lipofecting agents in vitro and are a promising basis for in vivo applications.

Item Type:Article
Subjects:Q Science > QH Natural history > QH301 Biology
Divisions:Department of Lipid Biochemistry
ID Code:1284
Deposited By: Ewa Swiezewska
Deposited On:03 Jan 2017 08:56
Last Modified:08 Mar 2018 15:34

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