title: Bis-quaternary gemini surfactants as components of nonviral gene delivery systems: a comprehensive study from physicochemical properties to membrane interactions.
abstract: Gemini surfactants have been successfully used as components of gene delivery systems. In the present work, a family of gemini surfactants, represented by the general structure [CmH2m+1(CH3)2N(+)(CH2)sN(+)(CH3)2CmH2m+1]2Br(-), or simply m-s-m, was used to prepare cationic gene carriers, aiming at their application in transfection studies. An extensive characterization of the gemini surfactant-based complexes, produced with and without the helper lipids cholesterol and DOPE, was carried out in order to correlate their physico-chemical properties with transfection efficiency. The most efficient complexes were those containing helper lipids, which, combining amphiphiles with propensity to form structures with different intrinsic curvatures, displayed a morphologically labile architecture, putatively implicated in the efficient DNA release upon complex interaction with membranes. While complexes lacking helper lipids were translocated directly across the lipid bilayer, complexes containing helper lipids were taken up by cells also by macropinocytosis. This study contributes to shed light on the relationship between important physico-chemical properties of surfactant-based DNA vectors and their efficiency to promote gene transfer, which may represent a step forward to the rational design of gene delivery systems.
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Department of Life Sciences, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Cardoso
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Department of Life Sciences, University of Coimbra, Coimbra, Portugal.
authors.forename: Catarina M
authors.initials: CM
authors.lastname: Morais
authors.affiliation: Centro de Investigação em Química, Department of Chemistry and Biochemistry, University of Porto, Porto, Portugal.
authors.forename: Sandra G
authors.initials: SG
authors.lastname: Silva
authors.affiliation: Centro de Investigação em Química, Department of Chemistry and Biochemistry, University of Porto, Porto, Portugal.
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Marques
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Department of Life Sciences, University of Coimbra, Coimbra, Portugal.
authors.forename: Maria C Pedroso
authors.initials: MC
authors.lastname: de Lima
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Department of Life Sciences, University of Coimbra, Coimbra, Portugal. Electronic address: asjurado@bioq.uc.pt.
authors.forename: Maria Amália S
authors.initials: MA
authors.lastname: Jurado
mesh_terms: D002462:Cell Membrane / Q000737:chemistry*; D002470:Cell Survival; D002627:Chemistry, Physical; D004247:DNA / Q000737:chemistry; D018014:Gene Transfer Techniques / Q000295:instrumentation*; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D010957:Plasmids; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D013501:Surface-Active Agents; D004247:DNA
keywords: Bis-quaternary gemini surfactant; Cell membrane interactions; Complex preparation; Physico-chemical characterization; Transfection efficiency