Construction of a Stimuli-Responsive DNAzyme-Braked DNA Nanomachine for the Amplified Imaging of miRNAs in Living Cells and Mice

Synthetic DNA motors have spurred considerable research interest as a way to interrogate biochemical processes that can further facilitate disease diagnosis. However, current direct sense-on-demand DNA motors are hampered by undesired signal leakage originating from their nonspecific stimulation prior to their arrival at target sites. Herein, we propose a DNAzyme-guided DNA amplification motor through the facile built-in of a stimuli-responsive DNAzyme brake to facilitate the in vivo sensitive imaging of biomarkers by minimizing the off-site signal leakage in living systems. To realize the on-site activation, the inactive DNAzyme DNA motor was encapsulated into the folate (FA)-modified zeolitic imidazolate framework-8 (ZIF-8)/poly(D,L-lactic-co-glycolic acid (PLGA) nanovesicles. The FA interaction-promoted tumor-cell-selective delivery and the pH-responsive disassembly of ZIF-8/PLGA permitted sufficient release of DNAzyme cofactors to achieve on-site stimulation of DNAzyme for restoring the temporally caged DNA amplification motor in tumor cells where the endogenous miRNA target was thus specifically and sensitively analyzed. By integration of the cell selective delivery and the site-specific stimulation, our DNAzyme-guided DNA motor can realize the reliable imaging of tumor cells and provide a new toolbox for disease diagnosis.