NIR-switched DNA tweezer enables reversible miRNA recognition with erasable signal for in vivo continuous imaging

Continuous monitoring of miRNA expression in vivo is crucial for understanding complex biological processes. However, current miRNA imaging probes suffer from irreversible responses, impairing their capabilities for real-time tracking concentration fluctuations. Here, we present a near-infrared regulated DNA tweezer (NIR-DNA tweezer) with reversible binding affinities to target miRNA. Self-quenched DNA tweezer is composed of BHQ3-labeled miRNA recognition strand and Cy5-labeled competitive strand, while competitive strand is embedded with azobenzene (Azo) to photo-switch the hybridization zones of DNA tweezer for reversible miRNA recognitions. NIR-DNA tweezer is obtained by conjugating DNA tweezer to upconversion nanoparticles, which is switched to "transit" status upon high-power 808-nm irradiation with <i>cis</i>-Azo to allow miRNA recognition with Cy5 fluorescence recovery. Upon low-power 808-nm irradiation, NIR-DNA tweezer is switched to "closed" status with <i>trans</i>-Azo to release miRNA and erase signal. The as-presented NIR-DNA tweezer achieves real-time in vivo tracing of miRNA expression fluctuations upon continuous chemotherapeutic drug and inhibitor treatments.