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. Angle-dependent dynamic light scattering measurements also reveal the presence of relaxation processes within complexes formed by DNA and oxidized BFDMA that are absent for complexes formed by DNA and reduced BFDMA. These results, when combined, reveal that the amphiphilic nature of reduced BFDMA leads to lipoplexes with physical properties resembling those formed by classical cationic lipids, whereas the interaction of oxidized BFDMA with DNA is similar to that of nonamphiphilic cationic molecules bearing multiple charges (e.g., spermidine). In particular, the negative zeta-potential and measurable presence of DNA chain dynamics within complexes formed by oxidized BFDMA and DNA indicate that these complexes are loosely packed with excess charge due to DNA in their outer regions. These results, when combined with additional measurements performed in OptiMEM reduced-serum cell culture medium, lead to the proposition that the strong dependence of transfection efficiency on the oxidation state of BFDMA, as reported previously, is largely a reflection of the substantial change in the zeta-potentials of these complexes with changes in the oxidation state of BFDMA.
Hays
Melissa E
ME
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Jewell
Christopher M
CM
Kondo
Yukishige
Y
Lynn
David M
DM
Abbott
Nicholas L
NL
D003198:Computer Simulation; D005296:Ferrous Compounds / Q000737:chemistry*; D015227:Lipid Peroxidation; D008956:Models, Chemical; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure*; D010316:Particle Size; D010957:Plasmids / Q000737:chemistry*; D055672:Static Electricity
D005296:Ferrous Compounds; C505027:bis-(11-ferrocenylundecyl)dimethylammonium bromide