title: Phototoxic aptamers selectively enter and kill epithelial cancer cells.
abstract: 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.
authors.affiliation: Ontario Cancer Institute, University Health Network, Ontario, Canada M5G 2M9.
authors.forename: Cátia S M
authors.initials: CS
authors.lastname: Ferreira
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Cheung
authors.forename: Sotiris
authors.initials: S
authors.lastname: Missailidis
authors.forename: Stuart
authors.initials: S
authors.lastname: Bisland
authors.forename: Jean
authors.initials: J
authors.lastname: Gariépy
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D006224:Cricetinae; D006801:Humans; D008027:Light; D018396:Mucin-1 / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D011166:Porphyrins / Q000008:administration & dosage; D020033:Protein Isoforms / Q000378:metabolism; D052156:SELEX Aptamer Technique
chemical_list: D052157:Aptamers, Nucleotide; D002735:Chlorophyllides; D018396:Mucin-1; D017319:Photosensitizing Agents; D011166:Porphyrins; D020033:Protein Isoforms; C062985:phytochlorin