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
Permanent lenke
http://hdl.handle.net/11250/2359461Utgivelsesdato
2012Metadata
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- Institutt for kjemi [1404]
- Publikasjoner fra CRIStin - NTNU [38672]
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.