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Molecules 2012, 17(3), 3484-3500; doi:10.3390/molecules17033484
Article

Synthesis and Preliminary Investigations of the siRNA Delivery Potential of Novel, Single-Chain Rigid Cationic Carotenoid Lipids

1,†,* , 2,†, 3, 1, 1, 1, 2, 2, 2, 4, 3 and 3
1 Pre-Medical Unit, Weill Cornell Medical College in Qatar, Doha, P.O. Box 24144, Qatar 2 Research Division, Weill Cornell Medical College in Qatar, Doha, P.O. Box 24144, Qatar 3 Department of Chemistry, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway 4 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 / Revised: 12 March 2012 / Accepted: 12 March 2012 / Published: 16 March 2012
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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 carotenoid lipids; single-chain; rigid; cationic; non-viral siRNA delivery
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

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