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  • Hydrophobic moiety of cationic lipids strongly modulates their transfection activity.

Hydrophobic moiety of cationic lipids strongly modulates their transfection activity.

Molecular pharmaceutics (2009-04-04)
Rumiana Koynova, Boris Tenchov, Li Wang, Robert C Macdonald
ABSTRACT

Synthetic cationic lipids are widely used components of nonviral gene carriers, and the factors regulating their transfection efficiency are the subject of considerable interest. In view of the important role that electrostatic interactions with the polyanionic nucleic acids play in formation of lipoplexes, a common empirical approach to improving transfection has been the synthesis and testing of amphiphiles with new versions of positively charged polar groups, while much less attention has been given to the role of the hydrophobic lipid moieties. On the basis of data for approximately 20 cationic phosphatidylcholine (PC) derivatives, here we demonstrate that hydrocarbon chain variations of these lipids modulate by over 2 orders of magnitude their transfection efficiency. The observed molecular structure-activity relationship manifests in well-expressed dependences of activity on two important molecular characteristics, chain unsaturation and total number of carbon atoms in the lipid chains, which is representative of the lipid hydrophobic volume and hydrophilic-lipophilic ratio. Transfection increases with decrease of chain length and increase of chain unsaturation. Maximum transfection was found for cationic PCs with monounsaturated 14:1 chains. It is of particular importance that the high-transfection lipids strongly promote cubic phase formation in zwitterionic membrane phosphatidylethanolamine (PE). These remarkable correlations point to an alternative, chain-dependent process in transfection, not related to the electrostatic cationic-anionic lipid interactions.

MATERIALS
Product Number
Brand
Product Description

Avanti
14:1 EPC (Tf Salt), Avanti Research - A Croda Brand 890717O
Avanti
12:0 EPC (Cl Salt), Avanti Research - A Croda Brand 890700P, powder
Avanti
18:0 EPC (Cl Salt), Avanti Research - A Croda Brand 890703C
Avanti
18:0 EPC (Cl Salt), Avanti Research - A Croda Brand 890703P, powder
Avanti
14:0 EPC (Cl Salt), Avanti Research - A Croda Brand
Avanti
16:0-18:1 EPC (Cl Salt), Avanti Research - A Croda Brand 890705C
Avanti
16:0-18:1 EPC (Cl Salt), Avanti Research - A Croda Brand 890705P, powder
Avanti
16:0 EPC (Cl Salt), Avanti Research - A Croda Brand 890702P, powder
Avanti
18:1 EPC (Cl Salt), Avanti Research - A Croda Brand 890704C
Avanti
18:1 EPC (Cl Salt), Avanti Research - A Croda Brand