Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 59, Issue 8, Pages 782-797Publisher
ELSEVIER
DOI: 10.1016/j.addr.2007.06.006
Keywords
A/B toxins; Caveolae; endoplasmic reticulum; golgi apparatus; lipid rafts; Lysosomes; receptor-mediated endocytosis; retrograde-trafficking pathway; Shiga/Shiga-like toxin; targeted drug delivery
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Funding
- NIGMS NIH HHS [U54 GM105814, R01 GM065233-02, R01 GM065233-01, R01 GM065233] Funding Source: Medline
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The targeted delivery of drugs to the cell interior can be accomplished by taking advantage of the various receptor-mediated endocytic pathways operating in a particular cell. Among these pathways, the retrograde trafficking pathway from endosomes to the Golgi apparatus, and endoplasmic reticulum is of special importance since it provides a route to deliver drugs bypassing the acid pH, hydrolytic environment of the lysosome. The existence of pathways for drug or antigen delivery to the endoplasmic reticulum and Golgi apparatus has been to a large extent an outcome of research on the trafficking of A/B type-bacterial or plant toxins such as Shiga toxin within the cell. The targeting properties of these toxins reside in their B subunit. In this article we present an overview of the multiplicity of pathways to deliver drugs intracellularly. We highlight the retrograde trafficking pathway illustrated by Shiga toxin and Shiga-like toxin, and the potential role of the B subunit of these toxins as carriers of drugs, antigens and imaging agents. (C) 2007 Elsevier B.V. All rights reserved.
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