pH-Stimulated Self-Locked DNA Nanostructure for the Effective Discrimination of Cancer Cells and Simultaneous Detection and Imaging of Endogenous Dual-MicroRNAs

In this study, a pH-stimulated self-locked DNA nanostructure (SLDN) was developed to efficiently distinguish cancer cells from other cells for the simultaneous detection and imaging of endogenous dual-microRNAs (miRNAs). Impressively, the SLDN was specifically unlocked in the acidic environment of cancer cells to form unlocked-SLDN to disengage the i-motif sequence with a labeled fluorophore for the recovery of a fluorescence signal, resulting in the differentiation of cancer cells from normal cells. Meanwhile, unlocked-SLDN could combine and recognize the targets miRNA-21 and miRNA-155 simultaneously to trigger the hybridization chain reaction (HCR) amplification for sensitive dual-miRNA detection, with detection limits of 1.46 pM for miRNA-21 and 0.72 pM for miRNA-155. Significantly, compared with the current miRNA imaging strategy based on the traditional DNA nanostructure, the strategy proposed here remarkably eliminates the interference of normal cells to achieve high-resolution colocation imaging of miRNAs in tumor cells with an ultralow background signal. This work provided a specific differentiation method for tumor cells to materialize sensitive biomarker detection and distinguishable high-definition live-cell imaging for precise cancer diagnosis and multifactor research of tumor progression.