Lipoplexes formed from sugar-based gemini surfactants undergo a lamellar-to-micellar phase transition at acidic pH. Evidence for a non-inverted membrane-destabilizing hexagonal phase of lipoplexes |
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Authors: | Luc Wasungu Marco Scarzello Dick Hoekstra |
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Affiliation: | a Department of Cell Biology/Section Membrane Cell Biology, University Medical Center Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands b Physical Organic Chemistry Unit, Stratingh Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands |
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Abstract: | The present study aims at a better understanding of the mechanism of transfection mediated by two sugar-based gemini surfactants GS1 and GS2. Previously, these gemini surfactants have been shown to be efficient gene vectors for transfection both in vitro and in vivo. Here, using Nile Red, a solvatochromic fluorescent probe, we investigated the phase behavior of these gemini surfactants in complexes with plasmid DNA, so-called lipoplexes. We found that these lipoplexes undergo a lamellar-to-non-inverted micellar phase transition upon decreasing the pH from neutral to mildly acidic. This normal (non-inverted) phase at acidic pH is confirmed by the colloidal stability of the lipoplexes as shown by turbidity measurements. We therefore propose a normal hexagonal phase, HI, for the gemini surfactant lipoplexes at acidic endosomal pH. Thus, we suggest that besides an inverted hexagonal (HII) phase as reported for several transfection-potent cationic lipid systems, another type of non-inverted non-bilayer structure, different from HII, may destabilize the endosomal membrane, necessary for cytosolic DNA delivery and ultimately, cellular transfection. |
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Keywords: | DNA, deoxyribonucleic acid lipoplexes, complexes of DNA with cationic lipids DOPE or PE, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine PC, 1,2-dioleoyl-sn-glycero-3-phosphocholine PS, 1,2-dioleoyl-sn-glycero-3-[phospho- smallcaps" >l-serine] DOTAP, N-[1-(2,3-dioleyl)propyl]-N,N,N-trimethylammonim chloride CTAB, cetyltrimethylammonium bromide EDLPC, ethyldilauroylphosphatidylcholine EDOPC, ethyldioleoylphosphatidylcholine SHN, sodium 3-hydroxy-2-naphthoate SAINT-2, N-methyl-4-(dioleyl)methylpyridinium chloride λmax emission, maximum emission wavelength SAXS, small angle X-ray scattering HEPES, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid MES, 2-[N-morpholino]ethanesulfonic acid HBS solution, HEPES buffered saline solution Lα, lamellar phase LI, micellar phase HII, inverted hexagonal phase HI, normal hexagonal phase |
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