Self-Protected DNAzyme Walker with a Circular Bulging DNA Shield for Amplified Imaging of miRNAs in Living Cells and Mice

Abnormal expression of miRNAs is often detected in various human cancers. DNAzyme machines combined with gold nanoparticles (AuNPs) hold promise for detecting specific miRNAs in living cells but show short circulation time due to the fragility of catalytic core. Using miRNA-21 as the model target, by introducing a circular bulging DNA shield into the middle of the catalytic core, we report herein a self-protected DNAzyme (E) walker capable of fully stepping on the substrate (S)-modified AuNP for imaging intracellular miRNAs. The DNAzyme walker exhibits 5-fold enhanced serum resistance and more than 8-fold enhanced catalytic activity, contributing to the capability to image miRNAs much higher than commercial transfection reagent and well-known FISH technique. Diseased cells can accurately be distinguished from healthy cells. Due to its universality, DNAzyme walker can be extended for imaging other miRNAs only by changing target binding domain, indicating a promising tool for cancer diagnosis and prognosis.