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Synthesis and Preliminary Investigations of the siRNA Delivery Potential of Novel, Single-Chain Rigid Cationic Carotenoid Lipids
Pre-Medical Unit, Weill Cornell Medical College in Qatar, Doha, P.O. Box 24144, Qatar
Research Division, Weill Cornell Medical College in Qatar, Doha, P.O. Box 24144, Qatar
Department of Chemistry, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway
Department of Chemistry, Chemical Biology & Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 29 February 2012; in revised form: 12 March 2012 / Accepted: 12 March 2012 / Published: 16 March 2012
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.