Journal
BIOCONJUGATE CHEMISTRY
Volume 19, Issue 11, Pages 2120-2128Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bc8002138
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Funding
- National Institutes of Health [1 R21 EB006168]
- National Science Foundation [CTS-0754921]
- Alfred P. Sloan Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [0754921] Funding Source: National Science Foundation
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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. Lipoplexes transformed in this manner mediate levels of cell transfection in vitro that are comparable to levels of transfection mediated by lipoplexes prepared by mixing DNA and reduced BFDMA. We demonstrate further that the chemical reduction of oxidized BFDMA leads to changes in the zeta potentials of these lipoplexes (e.g., from negative to positive). Characterization of lipoplex internalization using confocal microscopy demonstrated that these changes in zeta potential correlate to differences in the extents to which these lipoplexes are internalized by cells. These results provide a framework from which to interpret differences in cell transfection mediated by reduced and oxidized BFDMA. When combined, the results of this study suggest the basis of an approach that could be used to transform lipoplexes actively or on-demand and provide spatial and/or temporal control over the transfection of cells in a range of different fundamental and applied contexts.
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