Alternate routes for drug delivery to the cell interior: pathways to the Golgi apparatus and endoplasmic reticulum.
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.
Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Maria Teresa
MT
Tarragó-Trani
Brian
B
Storrie
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins / Q000378:metabolism / Q000493:pharmacokinetics; D002772:Cholera Toxin; D020755:Coat Protein Complex I / Q000378:metabolism*; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes; D042541:Intracellular Space / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008247:Lysosomes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D021382:Protein Sorting Signals; D021381:Protein Transport / Q000187:drug effects; D022622:Shiga Toxin 1; D022603:Shiga Toxins; D014281:Trihexosylceramides / Q000276:immunology / Q000378:metabolism; D021601:trans-Golgi Network / Q000737:chemistry / Q000378:metabolism
D000951:Antigens, Neoplasm; D001427:Bacterial Toxins; D020755:Coat Protein Complex I; D008081:Liposomes; D021382:Protein Sorting Signals; D022622:Shiga Toxin 1; D022603:Shiga Toxins; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D002772:Cholera Toxin