DNA Logic Nanodevices for the Sequential Imaging of Cancer Markers through Localized Catalytic Hairpin Assembly Reaction

Monitoring tumor biomarkers is crucial for cancer diagnosis, progression monitoring, and treatment. However, identifying single or multiple biomarkers with the same spatial locations can cause false-positive feedback. Herein, we integrated the DNA tetrahedron (DT) structures with logic-responsive and signal amplifying capability to construct transmembrane DNA logic nanodevices (TDLNs) for the in situ sequential imaging of transmembrane glycoprotein mucin 1 (MUC1) and cytoplasmic microRNA-21 (miR-21) to cell identifications. The TDLNs were developed by encoding two metastable hairpin DNAs (namely, H1 and H2) in a DT scaffold, in which the triggering toeholds of H1 for miR-21 were sealed by the MUC1-specific aptamer (MUC1-apt). The TDLNs not only had the function of signal amplification owing to the localized catalytic hairpin assembly (CHA) reaction through spatial constraints effect of DT structures but also performed an AND logic operation to output a green Cy3 signal in MCF-7 cells, where MUC1 protein and miR-21 were simultaneously expressed. These results showed that the newly developed TDLNs have better molecular targeting and recognition ability so as to be easily identify cell types and diagnose cancer early.