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Phototoxic aptamers selectively enter and kill epithelial cancer cells

Ferreira, Cátia S.M ; Cheung, Melissa C ; Missailidis, Sotiris ; Bisland, Stuart ; Gariépy, Jean

Nucleic acids research, 2009-02, Vol.37 (3), p.866-876 [Periódico revisado por pares]

England: Oxford University Press

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Título:
Phototoxic aptamers selectively enter and kill epithelial cancer cells
Autor: Ferreira, Cátia S.M ; Cheung, Melissa C ; Missailidis, Sotiris ; Bisland, Stuart ; Gariépy, Jean
Assuntos: Animals ; Aptamers, Nucleotide - chemistry ; Aptamers, Nucleotide - metabolism ; Aptamers, Nucleotide - radiation effects ; Carcinoma - drug therapy ; Carcinoma - metabolism ; Carcinoma - pathology ; Cell Death ; Cell Line, Tumor ; Cricetinae ; Humans ; Light ; Molecular Biology ; Mucin-1 - metabolism ; Photochemotherapy ; Photosensitizing Agents - administration & dosage ; Porphyrins - administration & dosage ; Protein Isoforms - metabolism ; SELEX Aptamer Technique
É parte de: Nucleic acids research, 2009-02, Vol.37 (3), p.866-876
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Descrição: 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.
Editor: England: Oxford University Press
Idioma: Inglês

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Phototoxic aptamers selectively enter and kill epithelial cancer cells

Ferreira, Cátia S.M ; Cheung, Melissa C ; Missailidis, Sotiris ; Bisland, Stuart ; Gariépy, Jean

England: Oxford University Press

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