Biophysical studies and intracellular destabilization of pH-sensitive liposomes

被引:32
作者
Van Bambeke, F
Kerkhofs, A
Schanck, A
Remacle, C
Sonveaux, E
Tulkens, PM
Mingeot-Leclercq, MP
机构
[1] UCL, B-1200 Brussels, Belgium
[2] Unite Pharmacol Cellulaire & Mol, Brussels, Belgium
[3] Unite Chim Phys Mol & Cristallog, Louvain, Belgium
[4] Unite Biol Anim, Biochim Cellulaire Lab, Louvain, Belgium
[5] Unite Chim Pharmaceut & Radiopharm, Brussels, Belgium
关键词
D O I
10.1007/BF02664772
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We examined changes in membrane properties upon acidification of dioleoylphosphatidylethanolamine/choleslerylhemisuccinate liposomes and evaluated their potential to deliver entrapped tracers in cultured macrophages. Membrane permeability was determined by the release of entrapped calcein or hydroxypyrene-l,3,6-trisulfonic acid (HPTS)-p-xylene-bis-pyridinium bromide (DPX); membrane fusion, by measuring the change in size of the liposomes and the dequenching of octadecylrhodamine-B fluorescence; and change in lipid organization, by P-31 nuclear magnetic resonance spectroscopy. Measurement of cell-associated fluorescence and confocal microscopy examination were made on cells incubated with liposomes loaded with HPTS or HPTS-DPX. The biophysical studies showed (i) a lipid reorganization from bilayer to hexagonal phase progressing from pH 8.0 to 5.0, (ii) a membrane permeabilization for pH <65, (iii) an increase in the mean diameter of liposomes for pH <6.0, and (iv) a mixing of liposome membranes for pH <5.7. The cellular studies showed (i) an uptake of the liposomes that were brought from pH 7.5-7.0 to 6.5-6.0 and (ii) a release of similar to 15% of the endocytosed marker associated with its partial release from the vesicles (diffuse localization). We conclude that the permeabilization and fusion of pH-sensitive liposomes occur as a consequence of a progressive lipid reorganization upon acidification. These changes may develop intracellularly after phagocytosis and allow for the release of the liposome content in endosomes associated with a redistribution in the cytosol.
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收藏
页码:213 / 223
页数:11
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