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

Abstract

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.

Simultaneous Response of Mitochondrial MicroRNAs to Identify Cell Apoptosis with Multiple Responsive Intelligent DNA Biocomputing Nanodevices

“…DNA biocomputing nanodevices (DBNs), owing to high programmability, multiple logic inputs, and good biocompatibility, have been widely applied in molecular imaging. − However, they suffer from seldom focusing on molecular events and poor spatial selectivity in tumor cells. − Furthermore, DNA logic nanodevices for spatially selective imaging of tumor cells have been initially tried and successfully constructed, but there are problems such as low detection sensitivity and slow operation.…”

MicroRNA Imaging Encounters Rolling Circle Amplification: Intracellular Na+-Fueled Linear Programmable DNAzyme Nanostructure

“…Additionally, the standard miRNA assay of RT-qPCR was used to quantify the different amounts of miR-21 in various cell lines in order to demonstrate the accuracy of our proposed method for monitoring the content of miR-21. All of the results were consistent with the previous report that the normal cell line L02 expresses a low level of miR-21, 39 whereas the cancer cell lines MCF-7 and HeLa express a higher level of miR-21, indicating that our method can discriminate between normal and cancer cells with high selectivity and has excellent application prospects in the early diagnosis of cancer.…”

A General Signal Amplifier of Self-Assembled DNA Micelles for Sensitive Quantification of Biomarkers

“…These nanostructures have excellent structural rigidity and programmable reaction sites. By assembling free DNA probes at suitable positions in these nanostructures, using the spatial confinement effect and three-dimensional nanostructures, DNA nanoprobes with excellent signal amplification ability have been developed. − However, these DNA nanostructures tend to be time-consuming to prepare and expensive due to the large number of long DNA strands required. In addition, the sequence requirements of these DNA nanostructures are quite strict, which greatly limits further applications in nanoprobe preparation.…”