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.
Keywords: carotenoid lipids; single-chain; rigid; cationic; non-viral siRNA delivery
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Pungente, M.D.; Jubeli, E.; Øpstad, C.L.; Al-Kawaz, M.; Barakat, N.; Ibrahim, T.; Khalique, N.A.; Raju, L.; Jones, R.; Leopold, P.L.; Sliwka, H.-R.; Partali, V. Synthesis and Preliminary Investigations of the siRNA Delivery Potential of Novel, Single-Chain Rigid Cationic Carotenoid Lipids. Molecules 2012, 17, 3484-3500.
Pungente MD, Jubeli E, Øpstad CL, Al-Kawaz M, Barakat N, Ibrahim T, Khalique NA, Raju L, Jones R, Leopold PL, Sliwka H-R, Partali V. Synthesis and Preliminary Investigations of the siRNA Delivery Potential of Novel, Single-Chain Rigid Cationic Carotenoid Lipids. Molecules. 2012; 17(3):3484-3500.
Pungente, Michael D.; Jubeli, Emile; Øpstad, Christer L.; Al-Kawaz, Mais; Barakat, Nour; Ibrahim, Tarek; Khalique, Nada Abdul; Raju, Liji; Jones, Rachel; Leopold, Philip L.; Sliwka, Hans-Richard; Partali, Vassilia. 2012. "Synthesis and Preliminary Investigations of the siRNA Delivery Potential of Novel, Single-Chain Rigid Cationic Carotenoid Lipids." Molecules 17, no. 3: 3484-3500.