Fusion cell-liposome

In principle, liposomes can enter (target) cells through different pathways by direct fusion of liposomes and the plasma membrane (1) or by an endo-cytic uptake mechanism. Other liposome-cell interactions that have been described in the literature are absorption, phospholipid and protein exchange, and cell-induced leakage of liposome contents (2,3). 

Stromberg, A., Karlsson, A., Ryttsen, F., Davidson, M., Chiu, D.T., Orwar, O., Microfluidic device for combinatorial fusion of liposomes and cells. Anal. Chem. 2001, 73, 126-130. 

In the case of red blood cells, it is assumed that the progressive loss of lipid asymmetry, possibly associated with the entry of calcium, is a signal that the cell is aging. This signal, in turn, is recognized by macrophages and leads to cell destruction. Dmgs which, for example, compete for calcium bound to phosphatidylserine could interfere with these processes and many other Ca2+-dependent processes such as protein kinase C activation. The influence of asymmetry in membranes of different phospholipid composition on the fusion of liposomes has been studied and reported [22]. 

Artificial cell models have been developed to help understand the membrane fusion process. A common model that involves vesicles containing channel proteins that are driven by osmotic pressure to fuse with a planar lipid bilayer was reported. A protein-free model has also been used to demonstrate transient opening of fusion pores. " Liposomes have been described as artificial cells and have also been used to examine membrane fusion. - Recently, an electroinjection technique has been developed, which makes it possible to form lipid nanotubes and networks between liposome reservoirs. - Here, we briefly present two models, recent advances in the development of a liposome-lipid nanotube network as an artificial cell model that mimics the latter stages of exocytosis for cell study and fusion of vesicles inside liposomes with a DNA zipper. 

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. 

Liposomes that remain impermeable to their contents cannot release these compounds without interaction with cells. This cellular interaction occurs by three different mechanisms (Fig. 11) [57], Of these, fusion and adsorption usually involve drug leakage, whereas effective drug delivery results from en-docytosis. 

Fusion of the liposome with the cell membrane. For this, the lipid portion of the vesicle becomes part of the cell wall. 

The concept of de-PEGylation can be applied to the development of nanoparticle-based drug delivery systems. PEG is used for the modification of liposomes to increase their blood circulation time [38], However, it also prevents cellular uptake, resulting in a decrease in therapeutic efficiency thus, modifications of the liposome surface with PEG interfere with membrane fusion to the cell membrane and liposome decomposition [39]. One of the possible strategies to solve this problem is to cleave the PEG chains after the nanoparticle reaches the target site (Fig. 9). This system of de-PEGylation of liposomes is also useful in avoiding the immune... 

Fig. 9 Utility of de-PEGylation technology in liposomes, (a) PEG derivative possessing a lipid moiety. The covalent bond between PEG and the lipid moiety can be cleaved by stimuli such as those within the acid environment of cancer and inflammation, (b) After binding the target cell via specific recognition of the receptor by the ligand, PEG molecules on the surface of the liposome are cleaved. The release of PEG facilitates membrane fusion of the liposome and liposome decomposition, resulting in efficient drug delivery...

Wrobel I, Collins D. Fusion of cationic liposomes with mammalian cells occurs after endocytosis. Biochim Biophys Acta 1995 1235(2) 296-304. 

Energy Dependence on Liposome Uptake and Fusion with Cell Membranes... 

Incubation at 4°C (see section Energy Dependence on Liposome Uptake and Fusion with Cell Membranes ) and a block of metabolic activity (see section Metabolic Activity ) might also be used to block endocytosis and to detect cellular association or fusion. 

Modification of Cells for Transport Experiments Experimental control of intracellular environment, 171, 817 implantation of isolated carriers and receptors into living cells by Sendai virus envelope-mediated fusion, 171, 829 resonance energy transfer microscopy visual colocalization of fluorescent lipid probes in liposomes, 171, 850. 

A quite different application of liposomes as reactive compartments is in the field of drug delivery. It was found several years ago that liposomes, because of their hydrophobic nature, strongly interact with the biological cell membrane and can actually be incorporated inside by endocytosis or other mechanisms, e.g., fusion (Allison and Gregoriadis, 1974 Gregoriadis, 1976a, b 1988 1995 Papa-hadjopoulus etah, 1989). 

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