Cytoplasm liposome fusion

The fusion of liposomes with cells is envisioned to deliver their contents directly to the cytoplasm [15,26]. However, whereas the fusion is an essential cellular process in endocytosis, it appears that the liposome fusion with the cells occurs very rarely and is enhanced by reconstitution of viral surface proteins. Therefore, it is apparent that this process is largely controlled by membrane protein of a cell or virus. This can be done not by a simple fusion of bilayers with cells but by incorporating fusogenic proteins or, in vitro, addition of fusogens. 

Ulvatne, H., Haukland, H. H., Olsvik, O., and Vorland, L. H. (2001). Lactoferricin B causes depolarization of the cytoplasmic membrane of Escherichia coli ATCC 25922 and fusion of negatively charged liposomes. FEES Lett. 492, 62-65. 

The transition from coated vesicle to early endosome is accompanied by acidification of the vesicular lumen that continues into the late endosomal and lysosomal compartments, reaching a final pH in the perinuclear lysosome of approximately 4.5. Such acidification associated with endosome maturation provides the means by which certain viruses gain access to the cytosol. Acid-induced conformational changes in the viral proteins trigger translocation across the endosomal membrane via a fusion process. By taking advantage of the endosomal acidification, pH-sensitive liposomes, adenovirus and endosomolytic peptides have been used to facilitate the release of plasmids into the cytoplasm prior to lysosomal degradation. 

Cationic lipids can destabilize a cellular membrane because of its intrinsic detergent property. Therefore, destabilization of endosomal and/or lysosomal membrane may be a contribution from the cationic lipids itself In the same context, it was shown that the cationic lipid/DOPE or cationic lipid/cholesterol liposome formulation exhibit surface anisotropies in terms of increased liposomal surface pH (161,162). The surface pH of the liposomal formulations exhibits at least two pH units higher than the pH of the solution at which they are made. Therefore, a liposomal solution made at physiological pH may in reality exhibit a surface pH > 9, which is detrimental for both the stability of endosome and activity of lysosomal enzymes. Endosomal disruptions were also done with fusogenic peptides, which promote pH-dependent fusion of small liposomes when associated with lipid bilayer. When these peptides were co-delivered with lipid/DNA complex, they imparted formidable endosomal disruption by changing its usual random coil conformation into amphipathic a-helix conformation at lower pH, resulting in consequent cytoplasmic delivery of DNA (163). 

FIG. 15 Cellular entry and intracellular kinetics of the cationic lipid-DNA complexes. Cationic lipid-DOPE liposomes form electrostatic complexes with DNA, and, in this case, also transferrin (Tf) is incorporated. Cellular uptake by endocytosis and endosomal acidification can be blocked with cytochalasin B and bafilomycin A, respectively. DNA is proposed to be released at the level of endosomal wall after fusion of the carrier lipids with endosomal bilayer. This process is facilitated by the formation of inverted hexagonal DOPE phase as illustrated in the lower corner on the right. After its release to the cytoplasm DNA may enter the nucleus. (From Ref. 253. By permission of Nature Publishing Group.)... 

Virosomes, which comprise liposomes with viral proteins such as Sendai virus hemagglutinin (HVJ liposomes). These complexes are thought to introduce DNA into the cytoplasm of the cell following hemaglutinin-mediated fusion of the liposome with the target cell membrane (43). 

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