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.