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Phototoxic aptamers selectively enter and kill epithelial cancer cells

Ferreira, Cátia S. M.; Cheung, Melissa C.; Missailidis, Sotiris; Bisland, Stuart and Gariépy, Jean (2009). Phototoxic aptamers selectively enter and kill epithelial cancer cells. Nucleic Acids Research, 37(3) pp. 866–876.

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The majority of cancers arise from malignant epithelial cells. We report the design of synthetic oligonucleotides (aptamers) that are only internalized by epithelial cancer cells and can be precisely activated by light to kill such cells. Specifically, phototoxic DNA aptamers were selected to bind to unique short O-glycan-peptide signatures on the surface of breast, colon, lung, ovarian and pancreatic cancer cells. These surface antigens are not present on normal epithelial cells but are internalized and routed through endosomal and Golgi compartments by cancer cells, thus providing a focused mechanism for their intracellular delivery. When modified at their 5′ end with the photodynamic therapy agent chlorin e6 and delivered to epithelial cancer cells, these aptamers exhibited a remarkable enhancement (>500-fold increase) in toxicity upon light activation, compared to the drug alone and were not cytotoxic towards cell types lacking such O-glycan-peptide markers. Our findings suggest that these synthetic oligonucleotide aptamers can serve as delivery vehicles in precisely routing cytotoxic cargoes to and into epithelial cancer cells.

Item Type: Journal Item
Copyright Holders: 2008 The Authors
ISSN: 1362-4962
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 26020
Depositing User: Sotiris Missailidis
Date Deposited: 08 Jan 2011 14:10
Last Modified: 02 May 2018 13:23
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