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Synthesis and preliminary investigations of the siRNA delivery potential of novel, single-chain rigid cationic carotenoid lipids

Pungente, Michael; Jubeli, Emile; Øpstad, Christer Lorentz; Al-Kawaz, Mais; Barakat, Nour; Ibrahim, Tarek; Abdul Khalique, Nada; Raju, Liji; Jones, Rachel; Leopold, Philip; Sliwka, Hans-Richard; Partali, Vassilia
Journal article, Peer reviewed
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molecules-17-03484.pdf (359.1Kb)
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http://hdl.handle.net/11250/2359461
Utgivelsesdato
2012
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  • Publikasjoner fra CRIStin - NTNU [26746]
Originalversjon
Molecules 2012, 17(3):3484-3500   10.3390/molecules17033484
Sammendrag
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.
Utgiver
MDPI
Tidsskrift
Molecules

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