Cationic Lipids: Molecular Structure/Transfection Activity Relationships and Interactions with Biomembranes

Efficient and non-toxic gene delivery by anionic lipoplexes based on polyprenyl ammonium salts and their effects on cell physiology

“…Moreover, positively‐charged polyprenyl‐based vectors meet the crucial requirement for interaction with the negatively‐charged phosphates on DNA: we demonstrated that efficient transfection was provided by negatively‐charged polyprenyl‐based lipoplexes. This finding is somewhat surprising because positively‐charged lipoplexes constitute the overwhelming majority of efficient nonviral vectors described in the literature and they are generally considered more efficient . The shift to a negative charge of lipid‐based vehicles after DNA condensation was originally assumed to ruin DNA protection and to inhibit cell association and entry.…”

“…Studies on polyisoprenoids strongly suggest that these long‐chain molecules, when present in the lipid bilayer, possess a specific coiled conformation and, consequently, the length of the hydrocarbon chain is much shorter than the predicted sum of respective C‐C bonds . Conflicting data exist on the influence of the lipoplex size on transfection efficiency and the optimal size has not been clearly defined so far . In our experiments, all of the lipoplexes were medium‐sized (200–300 nm) and highly effective, despite suggestions that such particles may be limited by diffusion and trigger worse cellular trafficking than larger lipoplexes .…”

Transitions between lamellar and nonlamellar phases in membrane lipids and their physiological roles

“…A large number of cationic amphiphiles have been synthesized and tested in transfection studies. Data on the relationships between transfection activity and cationic lipid molecular structure showed that the transfection activity depends in a systematic way on the lipid hydrocarbon chain structure 62,63 . Studies on a large series of cationic phosphatidylcholine derivatives have demonstrated that the transfection efficacy not only depends on the lipid hydrocarbon chain structure but also closely correlates with the propensity for non-lamellar phase formation in cationic phosphatidylcholine mixtures with membrane lipids.…”

“…Studies on a large series of cationic phosphatidylcholine derivatives have demonstrated that the transfection efficacy not only depends on the lipid hydrocarbon chain structure but also closely correlates with the propensity for non-lamellar phase formation in cationic phosphatidylcholine mixtures with membrane lipids. The data analysis shows that optimum transfection is displayed by lipids with chain length of ~14 carbon atoms and that the transfection efficiency strongly increases with an increase in chain unsaturation, specifically, upon replacement of saturated with monounsaturated chains [62][63][64] (Figure 4). …”

Cationic Liposomes in Different Structural Levels for Gene Delivery

“…Linker bonds are commonly ether, ester (Leventis & Silvius, 1990), amide (Behr et al, 1989) or urethane (or carbamate) groups (Koynova & Tenchov, 2010), but other groups such as redox-sensitive disulphide have also been employed ( Fig. 1.).…”