A Dual Endogenous Stimuli- Responsive Framework Nucleic Acid Nanodevice for MicroRNA Imaging

Framework nucleic acids (FNAs) have emerged as intelligent sensing systems for the detection of tumor-related biomarkers in living cells. However, orthogonally controlled manipulation of FNAs-based nanodevices for on-site imaging of microRNAs (miR-NAs) remains an intractable challenge. Herein, we report a dual endogenous stimuli-responsive FNA nanodevice that can perform miRNA sensing and imaging in a tumor-specific manner. The sensing function of the nanodevice is silent (OFF) by rationally incorporating adenosine 5'-triphosphate (ATP) aptamer and an abasic site, which can also be activated (ON) with ATP and human apurinic/apyrimidinic endonuclease 1 (APE1) in tumor cells, enabling on-site and efficient miRNA imaging with improved tumor specificity. Furthermore, we demonstrate the capability of the nanodevice for specific miRNA imaging both in living cells and in vivo based on the "dual keys" (overexpressed ATP and APE1 in tumors) priming mode. Therefore, this work illustrates a simple biosensing methodology with great potential for precise imaging of tumor biomarkers in clinical diagnosis and therapeutic evaluation.