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UW-Madison

  Abbott Research Group - UW Chemical and Biological Engineering

Laboratory for Molecular Engineering
Department of Chemical and Biological Engineering

Active Control of Surfactants


Demonstrated principles for active control of polymer- and DNA-lipid interactions using a family of ferrocene-based surfactants (JACS, 2005). Reversible control over microstructures formed by complexes of hydrophobically-modified polymers and surfactants was demonstrated Langmuir, 2005). A ferrocene-containing, redox-active cationic lipid has been shown to yield large differences in cell transfection depending on the oxidation state of the lipid (J. Controlled Release, 2006; Biophys J. 2007). The nanostructure of the DNA-lipid complexes was shown to be significantly different when changing this oxidation state (J. Phys Chem, 2008). The ability to activate lipoplexes toward transfection electrochemically and ‘on demand’ creates new opportunities to deliver DNA in vitro and in vivo with both spatial and temporal control.

Ferrocene-Containing Cationic Lipids: Influence of Redox State on Cell Transfection

Bis-(11-ferrocenylundecyl)dimethylammonium Bromide (BFDMA)
Bis-(11-ferrocenylundecyl)dimethylammonium Bromide (BFDMA)

Fluorescence microscopy images (10X) showing relative levels of EGFP expression in COS-7 cells transfected with pEGP-N1 and either (A) reduced BFDMA or (B) oxidized BFDMA at a lipid concentration of 10 M.
Fluorescence microscopy images (10X) showing relative levels of EGFP expression in COS-7 cells transfected with pEGP-N1 and either (A) reduced BFDMA or (B) oxidized BFDMA at a lipid concentration of 10 μM.


SANS spectra obtained using solutions of reduced (dark symbols, charge ratio 1.1:1) and oxidized (light symbols, charge ratio 3.3:1) BFDMA (1 mM) mixed with a solution of plasmid DNA (2.9 mg/mL).
SANS spectra obtained using solutions of reduced (dark symbols, charge ratio 1.1:1) and oxidized (light symbols, charge ratio 3.3:1) BFDMA (1 mM) mixed with a solution of plasmid DNA (2.9 mg/mL).

 

Cryo-TEM image of Lipoplexes formed in solutions containing 8 μM reduced BFDMA and 2.4 μg/ml DNA (charge ratio 1.1:1)
Cryo-TEM image of Lipoplexes formed in solutions containing 8 μM reduced BFDMA and 2.4 μg/ml DNA (charge ratio 1.1:1)

Acknowledgment: The cryo-TEM work was carried out in the Hannah and George Krumholz Laboratory for Advanced Microscopy, Part of the Technion Project on Complex Fluids, Microstructure and Macromolecules.

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