title: Structural and transfection properties of amine-substituted gemini surfactant-based nanoparticles.
abstract: BACKGROUND
  Increases in DNA transfection efficiencies for non-viral vectors can be achieved through rational design of novel cationic building blocks. Based on previous results examining DNA condensation by polyamines, novel gemini surfactants have been designed that incorporate aza or imino substituents within the spacer group in order to increase interactions with DNA and potentially improve their DNA transfection ability.
  
  
  METHODS
  Transfection efficiencies and cell toxicity of gemini nanoparticles constructed from plasmid DNA, gemini surfactant, and a neutral lipid were measured in COS7 cells using a luciferase assay. Structural properties of nanoparticles were examined by using circular dichroism, particle size, zeta potential, and small-angle X-ray scattering (SAXS) measurements.
  
  
  RESULTS
  The incorporation of aza and imino substituents within the spacer group was observed to enhance the transfection ability of gemini surfactants. Incorporation of an imino group in the structure of the 1,9-bis(dodecyl)-1,1,9,9-tetramethyl-5-imino-1,9-nonanediammonium dibromide surfactant (12-7NH-12) resulted in a statistically significant (p < 0.01) 9-fold increase in transfection compared to an unsubstituted gemini surfactant and a 3-fold increase compared to the corresponding aza-substituted compound. A pH-dependent transition in size and zeta potential was observed to occur at pH 5.5 for complexes formed from the 12-7NH-12 compound. SAXS results show weakly ordered structures and the presence of multiple phases.
  
  
  CONCLUSIONS
  The incorporation of a pH-active imino group within the spacer of the gemini surfactant results in a significant increase in transfection efficiency that can be related to both pH-induced changes in nanoparticle structure and the formation of multiple phases that more readily allow for membrane fusion that may facilitate DNA release.
authors.affiliation: School of Pharmacy, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada N2L 3G1.
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Wettig
authors.forename: Ildiko
authors.initials: I
authors.lastname: Badea
authors.forename: McDonald
authors.initials: M
authors.lastname: Donkuru
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Verrall
authors.forename: Marianna
authors.initials: M
authors.lastname: Foldvari
mesh_terms: D000588:Amines / Q000737:chemistry*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D008055:Lipids; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics*; D013500:Surface Tension; D013501:Surface-Active Agents / Q000737:chemistry*; D014162:Transfection
chemical_list: D000588:Amines; D008055:Lipids; D013501:Surface-Active Agents; D008156:Luciferases