title: Mesomorphic imidazolium salts: new vectors for efficient siRNA transfection.
abstract: The preparation of chloride (1(n)) and bromide (2(n)) derivatives of 1-methyl-3-[3,4-bis(alkoxy)benzyl]-4H-imidazolium with n = 6, 12, 16, 18 is described. The two series of salts possess a rich thermotropic mesomorphism, chain-length dependent. Thus, a lamellar smectic A phase, a bicontinuous cubic Ia3d phase, and a columnar hexagonal liquid crystalline mesophase are induced as a function of increasing chain length. The mesomorphic properties were studied by polarizing optical microscopy, differential scanning calorimetry, and X-ray diffraction, and with the support of dilatometry and molecular dynamics, models for the various supramolecular arrangements of the salts are proposed. Such cationic amphiphiles were expected to be candidate molecules to design a new delivery reagent for nucleic acid transfection, particularly for short interfering RNA (siRNA). The use of an RNA interference mechanism, by introduction into cells by transfection of chemically synthesized siRNAs, is a powerful method for gene silencing studies. To exploit the potential of these amphilic imidazolium salts, these molecules were formulated with cohelper lipids and tested for their efficacy to deliver active siRNAs. Our results show high transfection efficacy of our formulated compounds and high silencing efficiency with more than 80% inhibition of the targeted gene at 10 nM siRNA concentration. Taken together our results show the potency of amphiphilic imidazolium salts as a new generation of transfection reagents for RNA interference.
authors.affiliation: Institut de Physique et Chimie des Matériaux de Strasbourg, UMR 7504, CNRS-Université de Strasbourg, BP 43, 23 rue du Loess, F-67034 Strasbourg Cedex 2, France.
authors.forename: William
authors.initials: W
authors.lastname: Dobbs
authors.forename: Benoît
authors.initials: B
authors.lastname: Heinrich
authors.forename: Cyril
authors.initials: C
authors.lastname: Bourgogne
authors.forename: Bertrand
authors.initials: B
authors.lastname: Donnio
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Terazzi
authors.forename: Marie-Elise
authors.initials: ME
authors.lastname: Bonnet
authors.forename: Fabrice
authors.initials: F
authors.lastname: Stock
authors.forename: Patrick
authors.initials: P
authors.lastname: Erbacher
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Bolcato-Bellemin
authors.forename: Laurent
authors.initials: L
authors.lastname: Douce
mesh_terms: D002460:Cell Line; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D007202:Indicators and Reagents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D050866:Liquid Crystals / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D034741:RNA, Small Interfering / Q000378:metabolism*; D012492:Salts / Q000737:chemistry*; D014162:Transfection
chemical_list: D004337:Drug Carriers; D007093:Imidazoles; D007202:Indicators and Reagents; D034741:RNA, Small Interfering; D012492:Salts; C029899:imidazole