Wang Xing, Sun Hongzhi, Liu Bojun, Jiang Kemei, Li Zhaohui, Meng Hong-Min
College of Chemistry, Institute of Analytical Chemistry for Life Science, Henan Joint International Research Laboratory of Green Construction of Functional Molecules and Their Bioanalytical Applications, Zhengzhou Key Laboratory of Functional Nanomaterial and Medical Theranostic, Zhengzhou University, Zhengzhou 450001, China.
Anal Chem. 2022 Dec 13;94(49):17232-17239. doi: 10.1021/acs.analchem.2c03963. Epub 2022 Nov 28.
Taking advantage of the remarkable processivity and membrane penetrability, the gold nanoparticle (AuNP)-based three-dimensional (3D) DNA walking nanomachine has induced tremendous promise in molecular diagnostics and cancer therapy, whereas the executive ability of this nanomachine was eventually limited because of the disordered assembly between the walker and the track. Therefore, we developed a well-directed 3D DNA walking nanomachine by employing a DNA dendrimer as the track for intracellular imaging with high directionality and controllability. The nanomachine was constructed on a DNA dendrimer decorated with a substrate strand serving as the DNA track and a DNAzyme restrained by a locking strand as the walker. In this system, the distribution of the substrate strand and DNAzyme on the DNA dendrimer could be precisely regulated to achieve expected goals because of the specificity and predictability of the Watson-Crick base pairing, paving an explicit route for each walker to move along the track. Moreover, such a DNA dendrimer-based nanomachine owned prominent stability and anti-interference ability. By choosing microRNA-21 as a model analyte, the nanomachine was applied for the imaging of microRNA-21 in different cell lines and the monitoring of the dynamic microRNA-21 expression level in cancer cells. Therefore, we believe that this directed DNA walking nanomachine will have a variety of applications in molecular diagnostics and biological function modulation.
利用金纳米颗粒(AuNP)基三维(3D)DNA行走纳米机器卓越的持续合成能力和膜穿透性,其在分子诊断和癌症治疗方面展现出巨大潜力,然而由于行走体与轨道之间的无序组装,该纳米机器的执行能力最终受到限制。因此,我们通过采用DNA树枝状大分子作为轨道,开发了一种具有良好导向性的3D DNA行走纳米机器,用于细胞内成像,具有高方向性和可控性。该纳米机器构建在一个DNA树枝状大分子上,其上装饰有作为DNA轨道的底物链和由锁定链抑制的DNA酶作为行走体。在这个系统中,由于沃森-克里克碱基配对的特异性和可预测性,底物链和DNA酶在DNA树枝状大分子上的分布可以被精确调控以实现预期目标,为每个行走体沿着轨道移动铺平了明确的路径。此外,这种基于DNA树枝状大分子的纳米机器具有突出的稳定性和抗干扰能力。通过选择微小RNA-21作为模型分析物,该纳米机器被应用于不同细胞系中微小RNA-21的成像以及癌细胞中动态微小RNA-21表达水平的监测。因此,我们相信这种定向DNA行走纳米机器将在分子诊断和生物功能调节方面有多种应用。