Bacterial pore-forming hemolysins and their use in the cytosolic delivery of macromolecules

被引:44
作者
Provoda, CJ [1 ]
Lee, KD [1 ]
机构
[1] Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
关键词
cytosol; drug delivery; endocytosis; hemolysin; liposomes; Listeria monocytogenes; listeriolysin O; plasma membrane;
D O I
10.1016/S0169-409X(99)00067-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Advances in our understanding of fundamental cell biological processes have facilitated an expansion of therapeutic approaches to altering cellular physiology and phenotype. As many of these methods involve macromolecular agents that act on targets within the nucleus or cytoplasm, achieving their full potential ultimately requires the efficient delivery of these agents across the cell membrane barrier into the cytosol. Various strategies have been employed to enhance cytosolic delivery. These include either directly penetrating the plasma membrane, or avoiding degradation within the hydrolytic environment of the endosomal/lysosomal pathway after endocytic uptake. Some of the more promising methods in this regard have exploited the mechanisms utilized by certain viruses and bacteria for escaping into their host cell's cytosol. In this review, we will discuss some of these methods with an emphasis on the use of pore-forming proteins from bacteria. Particular attention will be drawn to the pH-sensitive endosomolytic bacterial hemolysins, such as listeriolysin O, and the potential for their use in cytosolic drug delivery systems. (C) 2000 Elsevier Science BN. All rights reserved.
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页码:209 / 221
页数:13
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