title: Di-Peptide-Modified Gemini Surfactants as Gene Delivery Vectors: Exploring the Role of the Alkyl Tail in Their Physicochemical Behavior and Biological Activity.
abstract: The aim of this work was to elucidate the structure-activity relationship of new peptide-modified gemini surfactant-based carriers. Glycyl-lysine modified gemini surfactants that differ in the length and degree of unsaturation of their alkyl tail were used to engineer DNA nano-assemblies. To probe the optimal nitrogen to phosphate (N/P) ratio in the presence of helper lipid, in vitro gene expression and cell toxicity measurements were carried out. Characterization of the nano-assemblies was accomplished by measuring the particle size and surface charge. Morphological characteristics and lipid organization were studied by small angle X-ray scattering technique. Lipid monolayers were studied using a Langmuir-Blodgett trough. The highest activity of glycyl-lysine modified gemini surfactants was observed with the 16-carbon tail compound at 2.5 N/P ratio, showing a 5- to 10-fold increase in the level of reporter protein compared to the 12 and 18:1 carbon tail compounds. This ratio is significantly lower compared to the previously studied gemini surfactants with alkyl or amino- spacers. In addition, the 16-carbon tail compound exhibited the highest cell viability (85%). This high efficiency is attributed to the lowest critical micelle concentration of the 16-tail gemini surfactant and a balanced packing of the nanoparticles by mixing a saturated and unsaturated lipid together. At the optimal N/P ratio, all nanoparticles exhibited an inverted hexagonal lipid assembly. The results show that the length and nature of the tail of the gemini surfactants play an important role in determining the transgene efficiency of the delivery system. We demonstrated here that the interplay between the headgroup and the nature of tail is specific to each series, thus in the process of rational design, the contribution of the latter should be assessed in the appropriate context.
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Mays A
authors.initials: MA
authors.lastname: Al-Dulaymi
authors.affiliation: Department of Chemical and Biological Engineering, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Jackson M
authors.initials: JM
authors.lastname: Chitanda
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Waleed
authors.initials: W
authors.lastname: Mohammed-Saeid
authors.affiliation: Department of Chemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Hessamaddin Younesi
authors.initials: HY
authors.lastname: Araghi
authors.affiliation: Department of Chemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Verrall
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.|Canadian Light Source, Saskatoon, Saskatchewan, Canada.
authors.forename: Pawel
authors.initials: P
authors.lastname: Grochulski
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. ildiko.badea@usask.ca.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Badea
mesh_terms: D000818:Animals; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D055598:Chemical Phenomena / Q000187:drug effects; D002522:Chlorocebus aethiops; D004151:Dipeptides / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D004151:Dipeptides; D013501:Surface-Active Agents; C035809:glycyllysine
keywords: gemini surfactants; gene delivery; non-viral vectors; packing parameter; small angle x-ray scattering