Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 10051, Taiwan.
ACS Nano. 2010 Mar 23;4(3):1433-42. doi: 10.1021/nn901374b.
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.
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效应而受到研究。在此，我们报告了一种使用 G-四链体作为药物载体靶向癌细胞进行光动力治疗（PDT）的新策略。一种能够形成 G-四链体的 AS1411 适体可以通过物理共轭将六个卟啉衍生物分子，5,10,15,20-四（1-甲基吡啶-4-基）卟啉（TMPyP4），与适体结合，形成适体-TMP 复合物。复合物中的 TMPyP4 分子通过嵌入和外部结合被鉴定为与适体紧密结合。由于众所周知 G-四链体结构可以靶向癌细胞中过表达的核仁素，因此在这项研究中，研究了 G-四链体结构作为载体通过核仁素介导的内吞作用将 TMPyP4 递送至癌细胞中的效果。结果表明，与 M10 正常上皮细胞相比，适体-TMP 复合物在 MCF7 乳腺癌细胞中表现出更高的 TMPyP4 积累。用光处理 180 s 后，MCF7 细胞中的光损伤大于 M10 细胞。这些结果表明，TMPyP4 的递呈和摄取是通过适体-TMP 复合物与细胞表面上的核仁素的特异性相互作用介导的，并且使用 AS1411 适体作为药物载体可能是癌症治疗中的一种潜在策略。
