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Intracellular drug delivery: Potential usefulness of engineered Shiga toxin subunit B for targeted cancer therapy
Vera Luginbuehl1, Nicolas Meier1, Karin Kovar1
1Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences, Grueental, P.O.X. 335, CH-8820 Waedenswil, Switzerland.
Abstract:
A treasure trove of intracellular cancer drug targets remains hidden behind cell membranes. However, engineered pathogen-derived toxins such as Shiga toxins can deliver small or macromolecular drugs to specific intracellular organelles. After binding to ganglioglobotriaosylceramide (Gb3, CD77), the non-toxic subunit B (StxB) of the Shiga-holotoxin is endocytosed and delivers its payload by a unique retrograde trafficking pathway via the endoplasmic reticulum to the cytosol. This review provides an overview of biomedical applications of StxB-based drug delivery systems in targeted cancer diagnosis and therapy. Biotechnological production of the Stx-material is discussed from the perspective of developing efficacious and safe therapeutics.
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