Delivery of Shiga Toxin 1 A Subunit into Epithelial Cells Using Silica-Based Nanowires

摘要

Silica-based nanowires were used to introduce the Shiga toxin 1 A subunit (StxAl) into bovine and human epithelial cells. We extended our previous technology, which employs fibronectin (Fn) as a ligand to induce integrin-mediated uptake of nanowires by coating nanowires with StxAl and Fn. Without its counterpart, B subunits, the protein synthesis inhibitor StxAl, cannot enter eukaryotic cells without the aid of Fn-coated nanowires. The bonding strengths of StxAl and Fn to the surface of nanowires were investigated by X-ray photoelectron spectroscopy. This technique demonstrated some complex interactions between Fn, StxAl, and the nanowires. Neutral red cytotoxicity assays and field emission scanning electron microscopy demonstrated that the StxAl-Fn-nanowire complexes were effectively internalized and resulted in epithelial cell death. This study shows that nanowires can be used to carry StxAl or potentially other toxic or therapeutic agents into eukaryotic cells. Ongoing studies are aimed toward specific cell targeting and increasing the functionality of the StxAl.