Aptamer-Based Tumor-Targeted Drug Delivery for Photodynamic Therapy
Aptamer-Based Tumor-Targeted Drug Delivery for Photodynamic Therapy
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DOI：
10.1021/nn901374b
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发表时间：
2010-03-01
期刊：
影响因子：
17.1
通讯作者：
Shieh, Ming-Jium
中科院分区：
文献类型：
--
作者：
Shieh, Yen-An;Yang, Shu-Jyuan;Shieh, Ming-Jium
一种特殊的富含G的DNA结构--G-四链体，因其特殊的物理特性和生物学效应而被研究。在这里，我们报告了一种新的策略，使用G-四链作为药物载体来靶向肿瘤细胞进行光动力治疗(PDT)。一个G-四链体形成的AS1411适配子可以与6个分子的卟啉衍生物5，10，15，20-tetrakis(1-methylpyridinium-4-yl)porphyrin(TMPyP4)物理偶联，形成APT-TMP络合物。该复合体中的TMPyP4分子以插层和外部结合的方式与适配子紧密结合。由于G-四链体结构被认为是针对癌细胞中过表达的核仁素的，因此本研究探讨了G-四链体结构作为载体通过核仁素介导的内化将TMPyP4运送到癌细胞中的作用。结果表明，APT-TMP复合体在MCF7乳腺癌细胞中的TMPyP4积聚高于在M10正常乳腺癌细胞中的积聚。光处理后，MCF7细胞的光损伤程度大于M10细胞。这些结果表明，TMPyP4的转运和摄取是由apt-TMP复合体与细胞表面核仁特异性相互作用介导的，AS1411适配子作为药物载体可能是一种潜在的癌症治疗策略。
A specialized G-rich DNA structure, G-quadruplex, has been studied for its special physical characteristics and biological effects. Herein we report a novel strategy of using G-quadruplex as a drug carrier to target cancer cells for photodynamic therapy (PDT). A G-quadruplex forming AS1411 aptamer could be physically conjugated with six molecules of porphyrin derivative, 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP4), to fabricate the apt-TMP complex. The TMPyP4 molecules in the complex were identified to bind tightly to the aptamer by intercalation and outside binding. Because the G-quadruplex structure is known to target the overexpressed nucleolin in cancer cells, in this study, the effect of the G-quadruplex structure as a carrier for the delivery of TMPyP4 into cancer cells by nucleolin-mediated internalization was investigated. The results showed that the apt-TMP complex exhibited a higher TMPyP4 accumulation in MCF7 breast cancer cells than in M10 normal epithelium cells. After treated with light for 180 s, the photodamage in MCF7 cells was larger than in M10 cells. These results indicated that the TMPyP4 delivery and uptake were mediated by the specific interaction of the apt-TMP complex with nucleolin on the cellular surface and that the use of the AS1411 aptamer as a drug carrier may be a potential tactic in cancer therapy.