Phototoxic aptamers selectively enter and kill epithelial cancer cells.
Phototoxic aptamers selectively enter and kill epithelial cancer cells.
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DOI：
10.1093/nar/gkn967
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发表时间：
2009-02
影响因子：
14.9
通讯作者：
Gariépy J
中科院分区：
文献类型：
--
作者：
Ferreira CS;Cheung MC;Missailidis S;Bisland S;Gariépy J
大多数癌症是由恶性上皮细胞引起的。我们报道了一种合成寡核苷酸(适配子)的设计，这种寡核苷酸只被上皮癌细胞内化，并可以被光精确激活以杀死这种细胞。具体地说，光毒DNA适配子被选择与乳腺、结肠、肺、卵巢和胰腺癌细胞表面独特的短O-糖肽信号结合。这些表面抗原不存在于正常的上皮细胞上，但被癌细胞内化并通过内体和高尔基体隔间传递，从而为它们在细胞内的传递提供了一种集中的机制。当用光动力疗法试剂氯化e6修饰其5‘端并传递给上皮癌细胞时，这些适配子在光激活时表现出显著的毒性增强(>；500倍增加)，与单独的药物相比，并且对缺乏这种O-糖肽标记的细胞类型没有细胞毒性。我们的发现表明，这些合成的寡核苷酸适配子可以作为运输工具，准确地将细胞毒货物运送到上皮癌细胞和进入上皮癌细胞。
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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