Abstract
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 cis-Azo to allow miRNA recognition with Cy5 fluorescence recovery. Upon low-power 808-nm irradiation, NIR-DNA tweezer is switched to "closed" status with trans-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.