A hierarchically programmable DNA nanodevice for spatiotemporally selective imaging of mitochondrial microRNA in cells and animals

Abstract

DNA nanodevices remain at the forefront of bioimaging efforts within living cells, yet most are constrained by the undesired off-site activation and the insufficient subcellular precision. Herein, we sought to overcome this limitation by developing a hierarchically programmable DNA nanodevice (HPDN) that enables spatiotemporally selective imaging of mitochondrial microRNA (miRNA) with improved detection accuracy. Specifically, the sensing function of HPDN is silent by the elaborate introduction of an abasic site and a photocleavable linker, but can be hierarchically activated by endogenous human apurinic/apyrimidinic endonuclease 1 (APE1) in the cytoplasm and exogenous ultraviolet light after targeted mitochondrial localization, allowing for mitochondria-specific miRNA imaging in cells and animals. It is demonstrated that the HPDN system promises a robust mitochondrial miRNA imaging with reduced off-tumor signal leakage, thus enhancing the tumor-to-background ratio. Moreover, this system is employed for the visualizing the APE1-mediated drug resistance in tumor cells, facilitating the advancement of tumor diagnosis and therapeutic evaluation. Therefore, this work illustrates a comprehensive and powerful biosensing toolbox with great potential for precise biomedical applications.