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Nucleic Acids Research Advance Access published online on December 22, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn967
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Phototoxic aptamers selectively enter and kill epithelial cancer cells

Cátia S. M. Ferreira1, Melissa C. Cheung1, Sotiris Missailidis2, Stuart Bisland1 and Jean Gariépy1,*

1Ontario Cancer Institute, University Health Network, Ontario, Canada M5G 2M9 and 2The Open University, Walton Hall, Milton Keynes, MK7 6AA, UK

*To whom correspondence should be addressed. Tel: +1 416 946 2967; Fax: +1 416 946 6529; Email: gariepy{at}uhnres.utoronto.ca

Received August 15, 2008. Revised November 13, 2008. Accepted November 14, 2008.

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.


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