CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China.
Department of Chemistry , University of Illinois at Urbana-Champaign , Urbana , Illinois 61801 , United States.
J Am Chem Soc. 2019 May 1;141(17):7056-7062. doi: 10.1021/jacs.9b01931. Epub 2019 Apr 15.
Nanodevices have potential as intelligent sensing systems for detection of microRNAs (miRNAs) in living cells. However, the resolution offered by "always active" nanodevices is often insufficient to manipulate miRNA sensing with high spatiotemporal control. In this work, using DNA nanotechnology we constructed an activatable DNA nanodevice programmed to detect miRNAs in vitro and in vivo with the high spatial and temporal precision of NIR light. Our nanodevice is functionalized on the surface of upconversion nanoparticles (UCNPs) with a rationally designed DNA beacon that displays UV light-activatable miRNA sensing activity. The UCNPs absorb deep-tissue-penetrable NIR light and emit high-energy UV light locally, which serve as transducers to operate the nanodevice in the NIR window. The nanodevice can naturally enter cells and enable remote regulation of its fluorescent imaging activity for miRNAs in living cells by NIR light illumination in a chosen place and time. Furthermore, we demonstrate that the nanodevice can be expanded to activatable imaging of intratumoral miRNAs in living mice. This work illustrates the potential of DNA nanodevices for miRNA detection with high spatiotemporal resolution, which could expand the toolbox of technologies for precise biological and medical analysis.
纳米器件有望成为用于检测活细胞中 microRNAs(miRNAs)的智能传感系统。然而,“始终活跃”的纳米器件提供的分辨率通常不足以实现对 miRNA 传感的高时空控制。在这项工作中,我们使用 DNA 纳米技术构建了一种可激活的 DNA 纳米器件,该器件可在体外和体内以近红外光的高精度时空控制来检测 miRNA。我们的纳米器件在上转换纳米粒子(UCNPs)的表面进行功能化,带有经过合理设计的 DNA 发夹,可显示出对 miRNA 具有 UV 光激活传感活性的 DNA 发夹。UCNPs 吸收可穿透深层组织的近红外光,并在局部发射高能 UV 光,这些光可作为传感器,在近红外窗口中操作纳米器件。纳米器件可以自然进入细胞,并通过在选定的位置和时间用近红外光照射来远程调节其对活细胞中 miRNA 的荧光成像活性。此外,我们证明该纳米器件可扩展为在活体小鼠的肿瘤内 miRNA 的可激活成像。这项工作说明了 DNA 纳米器件在具有高时空分辨率的 miRNA 检测方面的潜力,这可能会扩展用于精确生物学和医学分析的技术工具箱。