Chemical activation of lipoplexes formed from DNA and a redox-active, ferrocene-containing cationic lipid.

We recently reported that the ferrocene-containing cationic lipid BFDMA [bis(11-ferrocenylundecyl)dimethylammonium bromide] can be used to mediate cell transfection, and that levels of transfection depend critically upon the oxidation state of the ferrocenyl groups of the lipid. Here, we report that the redox activity of BFDMA can be exploited to transform lipoplexes formed from oxidized BFDMA (which do not transfect cells) to lipoplexes that are "active" (and thus mediate high levels of transgene expression) by treatment with the chemical reducing agent glutathione (GSH). We demonstrate that GSH can be used to reduce the ferrocenium groups of oxidized BFDMA rapidly both (i) in solution and (ii) in lipoplexes formed by mixing oxidized BFDMA and DNA.

Characterization of the nanostructure of complexes formed by a redox-active cationic lipid and DNA.

We report characterization of the nanostructures of complexes formed between the redox-active lipid bis(n-ferrocenylundecyl)dimethylammonium bromide (BFDMA) and DNA using small-angle neutron scattering (SANS) and cryogenic transmission electron microscopy (cryo-TEM). A particular focus was directed to the influence of lipid oxidation state (where reduced BFDMA has a net charge of +1 and oxidized BFDMA has a charge of +3) on the nanostructures of the solution aggregates formed. Complexes were characterized over a range of charge ratios of reduced BFDMA to DNA (1.

Lipoplexes formed by DNA and ferrocenyl lipids: effect of lipid oxidation state on size, internal dynamics, and zeta-potential.

The effect of lipid oxidation state on the physical properties of complexes formed by plasmid DNA and the redox-active lipid bis-(11-ferrocenylundecyl)dimethylammonium bromide (BFDMA) is reported. With increasing concentration of BFDMA, the hydrodynamic sizes of complexes formed by BFDMA and DNA (in the presence of 1 mM Li(2)SO(4)) pass through a maximum and the zeta-potential changes monotonically from -40 mV to +40 mV. In contrast, complexes formed by oxidized BFDMA and DNA exhibit a minimum in size and maintain a negative zeta-potential with increasing concentration of BFDMA.

Reversible condensation of DNA using a redox-active surfactant.

We report characterization of aqueous solutions of dilute Lambda phage DNA containing the redox-active surfactant (11-ferrocenylundecyl)trimethylammonium bromide (FTMA) as a function of the oxidation state of the FTMA. FTMA undergoes a reversible one-electron oxidation from a reduced state that forms micelles in aqueous solution to an oxidized state (containing the ferrocenium cation) that does not self-associate in solution. This investigation sought to test the hypothesis that FTMA can be used to achieve reversible control over the conformation of DNA-surfactant complexes in solution.

Ferrocene-containing cationic lipids for the delivery of DNA: oxidation state determines transfection activity.

The ability of two redox-active, ferrocene-containing cationic lipids [11-(ferrocenylundecyl)trimethylammonium bromide (FTMA) and bis(11-ferrocenylundecyl)dimethylammonium bromide (BFDMA)] to transfect mammalian cells was investigated. This study sought to determine the range of conditions over which these lipids were capable of transfecting cells and whether the oxidation state of the ferrocenyl groups in these materials could be used to influence the extent of transfection. Experiments conducted in the COS-7 cell line demonstrated that reduced and oxidized FTMA were substantially cytotoxic and did not transfect cells.

Electrochemical control of the interactions of polymers and redox-active surfactants.

We report the characterization of aqueous solutions (0.1 M Li(2)SO(4)) of dilute ethyl(hydroxyethyl) cellulose (EHEC) mixed with the redox-active surfactant (11-ferrocenylundecyl)trimethylammonium bromide (FTMA) by measurements of clouding temperatures and dynamic light scattering. The investigation sought to test the hypothesis that FTMA, which forms micelles in aqueous solution in its reduced state but not in its oxidized state, would permit reversible control over the formation of polymer-surfactant complexes in solution.

Ferrocene-containing cationic lipids: influence of redox state on cell transfection.

A ferrocene-containing, redox-active cationic lipid that can be transformed using electrochemical methods yields large differences in cell transfection depending on the oxidation state of the lipid. Expression of enhanced green fluorescent protein and firefly luciferase occurs at very high levels when DNA lipoplexes are formulated using the lipid in the reduced state. In contrast, transfection is negligible when oxidized lipid is used.