A near-infrared responsive photocaged amplified DNA nanodevice for precise and sensitive microRNA imaging

MicroRNAs (miRNAs) play a critical role in early cancer detection, but traditional DNA probes are limited by the low abundance of miRNAs and their "always effective" property. Herein, we construct a photocaged amplified DNA nanodevice (PAD) by attaching DNA probes to upconversion nanoparticles (UCs). Upon remote near-infrared (NIR) light stimulation, the photocleavable DNA probes are activated by emitted UV light, and subsequently triggered by target miRNA. This process is further propelled by mRNA and DNA hairpin to achieve "one to many" signal amplification, enabling precise and sensitive spatiotemporal resolved imaging of miRNA. <i>In vitro</i> results demonstrate that the proposed dual-cycle amplification strategy effectively prevents undesired activation and minimizes non-specific signals, achieving a remarkable 20-fold improvement in miRNA detection limit compared to the one-cycle amplification strategy. Additionally, PAD enables spatiotemporally controlled miRNA imaging in tumor-bearing mouse models through NIR light-regulated <i>in situ</i> activation. The proposed approach extends the application of light-gated spatiotemporal controllable DNA nanodevice in nucleic acid imaging, thereby advancing its application in biological and medical imaging.