Chemical oxidation of a redox-active, ferrocene-containing cationic lipid: Influence on interactions with DNA and characterization in the context of cell transfection

TitleChemical oxidation of a redox-active, ferrocene-containing cationic lipid: Influence on interactions with DNA and characterization in the context of cell transfection
Publication TypeJournal Article
Year of Publication2012
AuthorsAytar, BS, Muller, JPE, Golan, S, Kondo, Y, Talmon, Y, Abbott, NL, Lynn, DM
JournalJournal of Colloid and Interface Science
Volume387
Pagination56-64
Date PublishedDec
Type of ArticleArticle
ISBN Number0021-9797
Accession NumberWOS:000309572100006
Keywordsaqueous-solutions, Cationic lipids, Lipoplexes, DNA delivery, Nanostructure, Ferrocene, Complexes, drug, expression, gene delivery-systems, lipoplexes, liposomes, state, surfactants, vesicles
Abstract

We report an approach to the chemical oxidation of a ferrocene-containing cationic lipid [bis(11-ferrocenylundecyl)dimethylammonium bromide, BFDMA] that provides redox-based control over the delivery of DNA to cells. We demonstrate that BFDMA can be oxidized rapidly and quantitatively by treatment with Fe(III)sulfate. This chemical approach, while offering practical advantages compared to electrochemical methods used in past studies, was found to yield BFDMA/DNA lipoplexes that behave differently in the context of cell transfection from lipoplexes formed using electrochemically oxidized BFDMA. Specifically, while lipoplexes of the latter do not transfect cells efficiently, lipoplexes of chemically oxidized BFDMA promoted high levels of transgene expression (similar to levels promoted by reduced BFDMA). Characterization by SANS and cryo-TEM revealed lipoplexes of chemically and electrochemically oxidized BFDMA to both have amorphous nanostructures, but these lipoplexes differed significantly in size and zeta potential. Our results suggest that differences in zeta potential arise from the presence of residual Fe2+ and Fe3+. ions in samples of chemically oxidized BFDMA. Addition of the iron chelating agent EDTA to solutions of chemically oxidized BFDMA produced samples functionally similar to electrochemically oxidized BFDMA. These EDTA-treated samples could also be chemically reduced by treatment with ascorbic acid to produce samples of reduced BFDMA that do promote transfection. Our results demonstrate that entirely chemical approaches to oxidation and reduction can be used to achieve redox-based 'on/off' control of cell transfection similar to that achieved using electrochemical methods. (C) 2012 Elsevier Inc. All rights reserved.

Short TitleJ. Colloid Interface Sci.