Article

Alternate routes for drug delivery to the cell interior: pathways to the Golgi apparatus and endoplasmic reticulum.

Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Advanced Drug Delivery Reviews (impact factor: 11.5). 09/2007; 59(8):782-97. DOI:10.1016/j.addr.2007.06.006 pp.782-97
Source: PubMed

ABSTRACT 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.

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Keywords

A/B type-bacterial
 
acid pH
 
B subunit
 
cell interior
 
drugs
 
drugs bypassing
 
drugs intracellularly
 
endoplasmic reticulum
 
Golgi apparatus
 
hydrolytic environment
 
imaging agents
 
lysosome
 
multiplicity
 
particular cell
 
potential role
 
retrograde trafficking pathway
 
Shiga toxin
 
Shiga-like toxin
 
targeting properties
 
various receptor-mediated endocytic pathways