A novel cationic lipophosphoramide with diunsaturated lipid chains: synthesis, physicochemical properties, and transfection activities.
Cationic lipophosphoramidates constitute a class of cationic lipids we have previously reported to be efficient for gene transfection. Here, we synthesized and studied a novel lipophosphoramidate derivative characterized by an arsonium headgroup linked, via a phosphoramidate linker, to an unconventional lipidic moiety consisting of two diunsaturated linoleic chains. Physicochemical studies allowed us to comparatively evaluate the specific fluidity and fusogenicity properties of the liposomes formed. Although corresponding lipoplexes exhibited significant but relatively modest in vitro transfection efficiencies, they showed a remarkably efficient and reproducible ability to transfect mouse lung, with in vivo transfection levels higher than those observed with a monounsaturated analogue previously described. Thus, these results demonstrate that this diunsaturated cationic lipophosphoramidate constitutes an efficient and versatile nonviral vector for gene transfection. They also invite further evaluations of the transfection activity, especially in vivo, of gene delivery systems incorporating the lipid reported herein and/or other lipids bearing polyunsaturated chains.
Le Gall
Tony
T
INSERM U613, Université de Bretagne Occidentale, Brest, France.
Loizeau
Damien
D
Picquet
Erwan
E
Carmoy
Nathalie
N
Yaouanc
Jean-Jacques
JJ
Burel-Deschamps
Laure
L
Delépine
Pascal
P
Giamarchi
Philippe
P
Jaffrès
Paul-Alain
PA
Lehn
Pierre
P
Montier
Tristan
T
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D016880:Anisotropy; D001152:Arsenicals / Q000737:chemistry; D002412:Cations; D002460:Cell Line; D003102:Colloids; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008041:Linoleic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D010756:Phosphoric Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014162:Transfection; D019076:Transgenes
D000577:Amides; D001152:Arsenicals; D002412:Cations; D003102:Colloids; D008041:Linoleic Acids; D008081:Liposomes; D010756:Phosphoric Acids; D004247:DNA; C011067:phosphoramidic acid; D008156:Luciferases