title: Cationic amphiphiles with fatty acyl chain asymmetry of coconut oil deliver genes selectively to mouse lung.
abstract: Recent structure-activity studies have revealed a dramatic influence of hydrophobic chain asymmetry in enhancing gene delivery efficacies of synthetic cationic amphiphiles (Nantz, M. H. et al. Mol. Pharmaceutics2010, 7, 786-794; Koynova, R. et al. Mol. Pharmaceutics2009, 6, 951-958). The present findings demonstrate for the first time that such a transfection enhancing influence of asymmetric hydrocarbon chains observed in pure synthetic cationic amphiphiles also works for cationic amphiphiles designed with natural, asymmetric fatty acyl chains of a food-grade oil. Herein, we demonstrate that cationic amphiphiles designed with the natural fatty acyl chain asymmetry of food-grade coconut oil are less cytotoxic and deliver genes selectively to mouse lung. Despite lauroyl chains being the major fatty acyl chains of coconut oil, both the in vitro and In vivo gene transfer efficiencies of such cationic amphiphiles were found to be remarkably superior (>4-fold) to those of their pure dilauroyl analogue. Mechanistic studies involving the technique of fluorescence resonance energy transfer (FRET) revealed higher biomembrane fusibility of the cationic liposomes of the coconut amphiphiles than that of the symmetric dilauroyl analogue. AFM study revealed pronounced fusogenic nonlamellar structures of the liposomes of coconut amphiphiles. Findings in the FRET and cellular uptake study, taken together, support the notion that the higher cellular uptake resulting from the more fusogenic nature of the liposomes of coconut amphiphiles 1 are likely to play a dominant role in making the coconut amphiphiles transfection competent.
authors.affiliation: Division of Lipid Science and Technology, Indian Institute of Chemical Technology, Hyderabad, India.
authors.forename: Voshavar
authors.initials: V
authors.lastname: Chandrashekhar
authors.forename: Marepally
authors.initials: M
authors.lastname: Srujan
authors.forename: Rairala
authors.initials: R
authors.lastname: Prabhakar
authors.forename: Rakesh C
authors.initials: RC
authors.lastname: Reddy
authors.forename: Bojja
authors.initials: B
authors.lastname: Sreedhar
authors.forename: Kiran K R
authors.initials: KK
authors.lastname: Rentam
authors.forename: Sanjit
authors.initials: S
authors.lastname: Kanjilal
authors.forename: Arabinda
authors.initials: A
authors.lastname: Chaudhuri
mesh_terms: D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D055598:Chemical Phenomena; D000074263:Coconut Oil; D006224:Cricetinae; D003412:Cricetulus; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D010938:Plant Oils / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D008081:Liposomes; D010938:Plant Oils; D000074263:Coconut Oil