A Redox-Activatable DNA Nanodevice for Spatially-Selective, AND-Gated Imaging of ATP and Glutathione in Mitochondria.

Abstract

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.