Cargando…
Phototoxic aptamers selectively enter and kill epithelial cancer cells
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 t...
Autores principales: | , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647295/ https://www.ncbi.nlm.nih.gov/pubmed/19103663 http://dx.doi.org/10.1093/nar/gkn967 |
_version_ | 1782164915509788672 |
---|---|
author | Ferreira, Cátia S. M. Cheung, Melissa C. Missailidis, Sotiris Bisland, Stuart Gariépy, Jean |
author_facet | Ferreira, Cátia S. M. Cheung, Melissa C. Missailidis, Sotiris Bisland, Stuart Gariépy, Jean |
author_sort | Ferreira, Cátia S. M. |
collection | PubMed |
description | 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 e(6) 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. |
format | Text |
id | pubmed-2647295 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-26472952009-03-04 Phototoxic aptamers selectively enter and kill epithelial cancer cells Ferreira, Cátia S. M. Cheung, Melissa C. Missailidis, Sotiris Bisland, Stuart Gariépy, Jean Nucleic Acids Res Molecular Biology 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 e(6) 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. Oxford University Press 2009-02 2008-12-22 /pmc/articles/PMC2647295/ /pubmed/19103663 http://dx.doi.org/10.1093/nar/gkn967 Text en © 2008 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ 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. |
spellingShingle | Molecular Biology Ferreira, Cátia S. M. Cheung, Melissa C. Missailidis, Sotiris Bisland, Stuart Gariépy, Jean Phototoxic aptamers selectively enter and kill epithelial cancer cells |
title | Phototoxic aptamers selectively enter and kill epithelial cancer cells |
title_full | Phototoxic aptamers selectively enter and kill epithelial cancer cells |
title_fullStr | Phototoxic aptamers selectively enter and kill epithelial cancer cells |
title_full_unstemmed | Phototoxic aptamers selectively enter and kill epithelial cancer cells |
title_short | Phototoxic aptamers selectively enter and kill epithelial cancer cells |
title_sort | phototoxic aptamers selectively enter and kill epithelial cancer cells |
topic | Molecular Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647295/ https://www.ncbi.nlm.nih.gov/pubmed/19103663 http://dx.doi.org/10.1093/nar/gkn967 |
work_keys_str_mv | AT ferreiracatiasm phototoxicaptamersselectivelyenterandkillepithelialcancercells AT cheungmelissac phototoxicaptamersselectivelyenterandkillepithelialcancercells AT missailidissotiris phototoxicaptamersselectivelyenterandkillepithelialcancercells AT bislandstuart phototoxicaptamersselectivelyenterandkillepithelialcancercells AT gariepyjean phototoxicaptamersselectivelyenterandkillepithelialcancercells |