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.
College of Chemistry, Zhengzhou University, Zhengzhou 450001, China.
Nano Lett. 2021 Dec 8;21(23):10047-10053. doi: 10.1021/acs.nanolett.1c03732. Epub 2021 Nov 22.
Design of biosensors capable of imaging ATP and glutathione (GSH) in mitochondria remains a challenge, despite their importance in elucidating their correlated pathophysiological events. Here, we report a new strategy that uses redox-activatable aptamer sensor design combined with nanoparticle-based targeting capability to achieve spatially controlled, AND-gated imaging of ATP and GSH in mitochondria. The DNA nanodevice was designed by the controlled assembly of the redox-responsive ATP aptamer probe on the nanoparticles and further decorated with mitochondria-targeting signals. We demonstrate that the system allows for mitochondria-specific, correlated imaging of ATP and GSH in living cells and in vivo. Furthermore, because the system can be lighted up only when meeting the "dual keys" (overexpressed ATP and GSH in mitochondria) simultaneously, the DNA nanodevice enables specific imaging of tumors in vivo with improved tumor-to-normal tissue ratio. This work illustrates the potential of the DNA nanodevices in the imaging of mitochondrial multivariate targets.
尽管在阐明其相关病理生理事件方面具有重要意义，但能够对线粒体中的 ATP 和谷胱甘肽 (GSH) 进行成像的生物传感器的设计仍然是一个挑战。在这里，我们报告了一种新策略，该策略使用氧化还原反应激活适体传感器设计与基于纳米粒子的靶向能力相结合，以实现对线粒体中 ATP 和 GSH 的空间控制、与门成像。DNA 纳米器件是通过在纳米粒子上组装氧化还原响应性 ATP 适体探针，并进一步用线粒体靶向信号进行修饰来设计的。我们证明，该系统允许在活细胞和体内进行线粒体特异性、相关的 ATP 和 GSH 成像。此外，由于该系统只有在同时满足“双钥匙”（线粒体中过表达的 ATP 和 GSH）时才能被点亮，因此 DNA 纳米器件能够特异性地对体内肿瘤进行成像，提高了肿瘤与正常组织的比值。这项工作说明了 DNA 纳米器件在成像线粒体多变量靶标方面的潜力。
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