Hairpin cascade circuits on programmable DNA-nucleated spherical nucleic acid for intracellular targeted microRNA imaging

DNA molecular probes have been increasingly used for biological imaging and tumor theranostics. In particular, live-cell imaging of low abundance microRNA (miRNA) with high accuracy and efficiency was extremely important for understanding functions and dynamics of miRNA. Herein, an easy-to-obtain DNA-nucleated spherical nucleic acid (DSNA) was constructed by one pair of hairpin probes “sticked” on self-assembled three-dimensional (3D) urchin-like DNA nanostructures (UDNs) to realize sensitive imaging of tumor-related miRNA in living cells. UDNs were prepared through four short single-stranded DNA by a simple “one-pot” annealing process that took only a few minutes. Moreover, sticking the reactants of hairpin probes on the UDNs not only sped up the reaction kinetic rate, but also improved the sensitivity and efficiency of miRNA-triggered hairpin cascade circuits. Compared with traditional AuNP-based spherical nucleic acid, the DSNA possessed superb biocompatibility and stability, excellent cell internalization capability and accessibility, which endowed them tremendous advantages for the monitoring of miRNA in living cells. Therefore, our developed strategy exhibited great potential in sensitive imaging of intracellular miRNA, offering a new avenue for early tumor diagnosis and related biomedical research.