Trichain cationic lipids: the potential of their lipoplexes for gene delivery

Lajla Kudsiova, Atefeh Mohammadi, M. Firouz Mohd Mustapa, Frederick Campbell, Katharina Welser, Danielle Vlaho, Harriet Story, David J. Barlow, Alethea B. Tabor, Helen C. Hailes, Jayne M. Lawrence

Research output: Contribution to journalArticle

Abstract

Lipoplexes (LDs) have been prepared from DNA and positively charged vesicles composed of the helper lipid, dioleoyl L-α-phosphatidylethanolamine (DOPE) and either a dichain (DC) oxyethylated cationic lipid or their corresponding novel trichain (TC) counterpart. This is the first study using the TC lipids for the preparation of LDs and their application. Here the results of biophysical experiments characterising the LDs have been correlated with the in vitro transfection activity of the complexes. Photon correlation spectroscopy, zeta potential measurements and transmission electron microscopy studies indicated that, regardless of the presence of a third chain, there were little differences between the size and charge of the TC and DC containing LDs. Small angle neutron scattering studies established however that there was a significant conformational re-arrangement of the lipid bilayer when in the form of a LD complex as opposed to the parent vesicles. This re-arrangement was particularly noticeable in LDs containing TC lipids possessing a third chain of C12 or a longer chain. These results suggested that the presence of a third hydrophobic chain had a significant effect on lipid packing in the presence of DNA. Picogreen fluorescence and gel electrophoresis studies showed that the TC lipids containing a third acyl chain of at least C12 were most effective at complexing DNA while the TC lipids containing an octanoyl chain and the DC lipids were least effective. The transfection efficacies of the TC lipids in the form of LDs were found to be higher than for the DC analogues, particularly when the third acyl chain was an octanoyl or oleoyl moeity. Little or no increase in transfection efficiency was observed when the third chain was a methyl, acetyl or dodecanoyl group. The large enhancement in transfection performance of the TC lipids can be attributed to their ability to complex their DNA payload. These studies indicate that presence of a medium or long third acyl chain was especially beneficial for transfection.
Original languageEnglish
JournalBiomaterials Science
DOIs
Publication statusPublished - 16 Oct 2018

Keywords

  • gene delivery
  • trichain lipids
  • lipoplexes
  • Gene therapy

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    Kudsiova, L., Mohammadi, A., Mustapa, M. F. M., Campbell, F., Welser, K., Vlaho, D., Story, H., Barlow, D. J., Tabor, A. B., Hailes, H. C., & Lawrence, J. M. (2018). Trichain cationic lipids: the potential of their lipoplexes for gene delivery. Biomaterials Science. https://doi.org/10.1039/c8bm00965a