title: Chemical oxidation of a redox-active, ferrocene-containing cationic lipid: influence on interactions with DNA and characterization in the context of cell transfection.
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 Fe(2+) and Fe(3+) 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.
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, WI 53706, United States.
authors.forename: Burcu S
authors.initials: BS
authors.lastname: Aytar
authors.forename: John P E
authors.initials: JP
authors.lastname: Muller
authors.forename: Sharon
authors.initials: S
authors.lastname: Golan
authors.forename: Yukishige
authors.initials: Y
authors.lastname: Kondo
authors.forename: Yeshayahu
authors.initials: Y
authors.lastname: Talmon
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Abbott
authors.forename: David M
authors.initials: DM
authors.lastname: Lynn
mesh_terms: D000818:Animals; D019556:COS Cells; D002412:Cations / Q000737:chemistry; D002522:Chlorocebus aethiops; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry; D005296:Ferrous Compounds / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D000075163:Metallocenes; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D010084:Oxidation-Reduction; D014162:Transfection
chemical_list: D002412:Cations; D005290:Ferric Compounds; D005296:Ferrous Compounds; D008055:Lipids; D000075163:Metallocenes; D004247:DNA; C004998:ferrocene