title: Synthesis and preliminary investigations of the siRNA delivery potential of novel, single-chain rigid cationic carotenoid lipids.
abstract: The success of nucleic acid delivery requires the development of safe and efficient delivery vectors that overcome cellular barriers for effective transport. Herein we describe the synthesis of a series of novel, single-chain rigid cationic carotenoid lipids and a study of their preliminary in vitro siRNA delivery effectiveness and cellular toxicity. The efficiency of siRNA delivery by the single-chain lipid series was compared with that of known cationic lipid vectors, 3β-[N-(N',N'-dimethylaminoethane)carbamoyl]-cholesterol (DC-Chol) and 1,2-dimyristoyl-sn-glyceryl-3-phosphoethanolamine (EPC) as positive controls. All cationic lipids (controls and single-chain lipids) were co-formulated into liposomes with the neutral co-lipid, 1,2-dioleolyl-sn-glycerol-3-phosphoethanolamine (DOPE). Cationic lipid-siRNA complexes of varying (+/-) molar charge ratios were formulated for delivery into HR5-CL11 cells. Of the five single-chain carotenoid lipids investigated, lipids 1, 2, 3 and 5 displayed significant knockdown efficiency with HR5-CL11 cells. In addition, lipid 1 exhibited the lowest levels of cytotoxicity with cell viability greater than 80% at all (+/-) molar charge ratios studied. This novel, single-chain rigid carotenoid-based cationic lipid represents a new class of transfection vector with excellent cell tolerance, accompanied with encouraging siRNA delivery efficiency.
authors.affiliation: Pre-Medical Unit, Weill Cornell Medical College in Qatar, Doha, P.O. Box 24144, Qatar. mdp2001@qatar-med.cornell.edu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Pungente
authors.forename: Emile
authors.initials: E
authors.lastname: Jubeli
authors.forename: Christer L
authors.initials: CL
authors.lastname: Øpstad
authors.forename: Mais
authors.initials: M
authors.lastname: Al-Kawaz
authors.forename: Nour
authors.initials: N
authors.lastname: Barakat
authors.forename: Tarek
authors.initials: T
authors.lastname: Ibrahim
authors.forename: Nada
authors.initials: N
authors.lastname: Abdul Khalique
authors.forename: Liji
authors.initials: L
authors.lastname: Raju
authors.forename: Rachel
authors.initials: R
authors.lastname: Jones
authors.forename: Philip L
authors.initials: PL
authors.lastname: Leopold
authors.forename: Hans-Richard
authors.initials: HR
authors.lastname: Sliwka
authors.forename: Vassilia
authors.initials: V
authors.lastname: Partali
mesh_terms: D002338:Carotenoids / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005822:Genetic Vectors / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D008081:Liposomes / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D008956:Models, Chemical; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014162:Transfection
chemical_list: D008081:Liposomes; D034741:RNA, Small Interfering; D002338:Carotenoids