title: 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.
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, H(I), for the gemini surfactant lipoplexes at acidic endosomal pH. Thus, we suggest that besides an inverted hexagonal (H(II)) phase as reported for several transfection-potent cationic lipid systems, another type of non-inverted non-bilayer structure, different from H(II), may destabilize the endosomal membrane, necessary for cytosolic DNA delivery and ultimately, cellular transfection.
authors.affiliation: Department of Cell Biology/Section Membrane Cell Biology, University Medical Center Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Luc
authors.initials: L
authors.lastname: Wasungu
authors.forename: Marc C A
authors.initials: MC
authors.lastname: Stuart
authors.forename: Marco
authors.initials: M
authors.lastname: Scarzello
authors.forename: Jan B F N
authors.initials: JB
authors.lastname: Engberts
authors.forename: Dick
authors.initials: D
authors.lastname: Hoekstra
mesh_terms: D004247:DNA / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D005947:Glucose / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000737:chemistry*; D008358:Mannose / Q000737:chemistry; D008823:Micelles; D008958:Models, Molecular; D010078:Oxazines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D011726:Pyridinium Compounds / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D008081:Liposomes; D008823:Micelles; D010078:Oxazines; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D011726:Pyridinium Compounds; C414306:SAINT 2; D013501:Surface-Active Agents; D004247:DNA; D005947:Glucose; C044808:nile red; D008358:Mannose