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Fusogenic Liposomes as Nano Carriers for Biopolymer Delivery in Living Mammalian Cells

Fusionsliposomen zum Einbringen von Biopolymeren in lebenden Zellen

Living cells after treatment with fusogenic liposomes

Based on their highly bioavailable components, phospholipid vesicles (liposomes) are widely used e.g. for cell tracking, for non viral gene transfer (transfection), or for drug delivery. Their cellular uptake has been intensely investigated and shows a strong preference of endocytotic cellular uptake over fusion or lipid mediated poration of the plasma membrane. Unfortunately, endocytotic pathways go along with limited efficiencies, often below 1%. Increasing efficiencies is therefore of major importance.
In our lab we developed a simple and almost universal fusogenic liposome system containing neutral and positively charged lipid molecules as well as an additional lipid component with an extended conjugated π-electron system. The liposomes fuse very efficiently with living cell membranes with barely any toxic side effects. As fusion mechanism, we hypothesize that positively charged lipids and the delocalized electron system of the aromatic group interact synergetically to induce local dipoles and membrane instabilities. However, the exact mechanism is not yet understood.
This new type of fusogenic liposomes opens up a large number of biotechnological application fields. Fluorescent membrane labeling is only one of the numerous possible cell membrane modifications. With addition of other functionalized molecules like chelator lipids, biotinylated or antigenic lipids, surface functionalization of living cells can be achieved as well. This membrane modification can be extended in an additional step by protein coupling to the cell surface. Furthermore, cellular proteins as well as nucleotides or cancer therapeutics can be incorporated into fusogenic liposomes and via them, into living cells as well.

For more information please contact Dr. Agnes Csiszár (a.csiszar@fz-juelich.de)/ Dr. Bernd Hoffmann (b.hoffmann@fz-juelich.de)

Fusogenic Liposomes as Nanocarriers for the Delivery of Intracellular Proteins
Kube S, Hersch N, Naumovska E, Gensch T, Hendriks J, Franzen A, Landvogt L, Siebrasse JP, Kubitscheck U, Hoffmann B, Merkel R, Csiszár A.
Langmuir. 2017 Jan 31;33(4):1051-1059. doi: 10.1021/acs.langmuir.6b04304.

A bioanalytical assay to distinguish cellular uptake routes for liposomes
Braun T, Kleusch C, Naumovska E, Merkel R, Csiszár A.
Cytometry A. 2016 Mar;89(3):301-8. doi: 10.1002/cyto.a.22792.

Biotin-conjugated fusogenic liposomes for high-quality cell purification
Hersch N, Wolters B, Ungvari Z, Gautam T, Deshpande D, Merkel R, Csiszar A, Hoffmann B, Csiszár A.
J Biomater Appl. 2016 Jan;30(6):846-56. doi: 10.1177/0885328215603026.

Plasma membrane functionalization using highly fusogenic immune activator liposomes
Naumovska E, Ludwanowski S, Hersch N, Braun T, Merkel R, Hoffmann B, Csiszár A.
Acta Biomater. 2014 Mar;10(3):1403-11. doi: 10.1016/j.actbio.2013.12.009.

Fluorescent lipids: functional parts of fusogenic liposomes and tools for cell membrane labeling and visualization
Kleusch C, Hersch N, Hoffmann B, Merkel R, Csiszár A.
Molecules. 2012 Jan 20;17(1):1055-73. doi: 10.3390/molecules17011055.

Novel Fusogenic Liposomes for Fluorescent Cell Labeling and Membrane Modification.
Csiszár A. Hersch N., Dieluweit S., Biehl R., Merkel R., and Hoffmann B.
Bioconjugate Chemistry, 2010, 21 (3), 537-543. doi: 10.1021/bc900470y.