Three-dimensional ordered DNA network constructed by a biomarker pair for accurate monitoring of colorectal cancer

Precise and early screening of colorectal cancer (CRC) is one crucial yet challenging task for its treatment, and the analysis of multi-targets of CRC in a single assay with high accuracy is essential for pathological research and clinical diagnosis. Here, a CRC-related biomarker pair, microRNA-211 (miRNA-211) and H₂S, was detected by constructing a three-dimensional (3D) ordered DNA network. First, trace amount of miRNA-211 could initiate a hybridization chain reaction-based amplification process. A highly ordered 3D DNA network was formed based on the organized assembly of DNA-cube frameworks that were constructed by DNA origamis and Ag nanoparticles (NPs) encapsulated inside. In the presence of the H₂S, Ag NPs within the network can be etched to generate Ag₂S quantum dots, which could be better visualized in fluorescence in situ cell imaging. Using the 3D DNA ordered network as the sensing platform, it can acquire dual analysis of biomolecule (miRNA-211) and inorganic gas (H₂S) in vitro, overcoming the limitations of single type of biomarker detection in a single assay. This assay achieved a wide linearity range of H₂S from 0.05 to 10 μM, and exhibited a low limit of detection of 4.78 nM. This strategy allows us to acquire the spatial distributions of H₂S and miRNA expression levels in living CRC cells simultaneously, providing a highly sensitive and selective tool for early screening and monitoring of CRC.