Designing DNAzyme-Powered Nanomachines Simultaneously Responsive to Multiple MicroRNAs

Designing DNAzyme-Powered Nanomachines Simultaneously Responsive to Multiple MicroRNAs
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设计同时响应多个 MicroRNA 的 DNAzyme 驱动的纳米机器

DOI:
10.1002/chem.201804127
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发表时间:
2018
期刊:
Chemistry - A European Journal
影响因子:
--
通讯作者:
Zhou Rongxing
Zhou Rongxing
中科院分区:
其他
文献类型:
--
作者:
Zhong Xiaoxi;Yang Sishu;Yang Peng;Du Huan;Hou Xin;Chen Junbo;Zhou Rongxing

文献摘要

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在此,设计了一种DNAzyme驱动的纳米机器,以响应来自临床样本的多个肝细胞癌相关miRNAs。首先,用染料分子[荧光素、四甲基罗丹明和花菁 5(Cy5)]标记的DNARNA嵌合底物和相应miRNAs靶标的特异性识别探针构建了三种类型的纳米机器。一旦目标miRNAs被两个识别探针捕获,DNA纳米机器就被启动,导致DNA酶与底物之间的杂交。在辅因子的帮助下,纳米机器的自动操作是由DNA酶的循环切割驱动的。同时,我们还探索了识别探针与靶miRNA之间的识别行为。随后,这些以DNAzyme为动力的纳米机器被开发出来,用于在Femtomloar水平上均匀和同时检测三个目标miRNAs。此外,通过在实际临床样本中成功地检测到目标miRNA,证明了该方法在临床诊断中的潜力。因此,这种基于纳米机器的策略具有成为miRNA分析方法学创新的巨大潜力。
Herein, a DNAzyme‐powered nanomachine responsive to multiple hepatocellular carcinoma (HCC)‐related miRNAs derived from clinical samples was designed. Initially, three types of nanomachines were constructed with dye molecule [(fluorescein (FAM), tetramethylrhodamin (TMR), and Cyanine 5 (Cy5)]‐labeled DNA–RNA chimeric substrates and a specific recognized probe for the corresponding miRNAs target. Once the target miRNAs were captured by two recognizing probes, the DNA nanomachine was initiated, leading to the hybridization between the DNAzyme and the substrates. With the help of a cofactor, the automatic operation of the nanomachine was driven by cyclic cleavage of the DNAzyme. Meanwhile, we also explored the recognition behavior between the recognizing probe and the target miRNA. Subsequently, these DNAzyme‐powered nanomachines were developed for the homogeneous and simultaneous detection of three target miRNAs at the femtomloar level. Furthermore, the potential in clinical diagnosis was proven by the successful determination of target miRNA in real clinical samples. Thus, this nanomachine‐based strategy possesses significant potential to be an innovation in miRNA analysis methodology.