Characterization of the Nanostructure of Complexes Formed by a Redox-Active Cationic Lipid and DNA

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• 作者：Claire L. Pizzey ; Christopher M. Jewell ; Melissa E. Hays ; David M. Lynn ; Nicholas L. Abbott ; Yukishige Kondo ; Sharon Golan ; Yeshayahu Talmon
• 刊名：Journal of Physical Chemistry B
• 出版年：2008
• 出版时间：May 8, 2008
• 年：2008
• 卷：112
• 期：18
• 页码：5849 - 5857
• 全文大小：826K
• 年卷期：v.112,no.18(May 8, 2008)
• ISSN：1520-5207

文摘

We report characterization of the nanostructures of complexes formed between the redox-active lipid bis(n-ferrocenylundecyl)dimethylammonium bromide (BFDMA) and DNA using small-angle neutron scattering(SANS) and cryogenic transmission electron microscopy (cryo-TEM). A particular focus was directed to theinfluence of lipid oxidation state (where reduced BFDMA has a net charge of +1 and oxidized BFDMA hasa charge of +3) on the nanostructures of the solution aggregates formed. Complexes were characterized overa range of charge ratios of reduced BFDMA to DNA (1.1:1, 2.75:1, and 4:1) in solutions of 1 mM Li₂SO₄.For these complexes, a single peak in the SANS data at 1.2 nm^-1 indicated that a nanostructure with a periodicityof 5.2 nm was present, similar to that observed with complexes of the classical lipids DODAB/DOPE andDNA (multilamellar spacing of 7.0 nm). The absence of additional Bragg peaks in all the SANS data indicatedthat the periodicity did not extend over large distances. Both inverse Fourier transform analysis and formfactor fitting suggested formation of a multilamellar vesicle. These results were confirmed by cryo-TEMimages in which multilamellar complexes with diameters between 50 and 150 nm were observed with nomore than seven lamellae per aggregate. In contrast to complexes of reduced BFDMA and DNA, Braggpeaks were absent in SANS spectra of complexes formed by oxidized BFDMA and DNA at all charge ratiosinvestigated. The low-q behavior of the SANS data obtained using oxidized BFDMA and DNA complexessuggested that large, loose aggregates were formed, consistent with complementary cryo-TEM images showingpredominantly loose disordered aggregates. Some highly ordered spongelike and cubic phase nanostructureswere also detected in cryo-TEM images. We conclude that control of BFDMA oxidation state can be used tomanipulate the nanostructures of lipid-DNA complexes formed using BFDMA.