Spatiotemporally Controlled Ultrasensitive Molecular Imaging Using a DNA Computation-Mediated DNAzyme Platform

Programming ultrasensitive and stimuli-responsive DNA-zyme-based probes that contain logic gate biocomputation hold great potential for precise molecular imaging. In this work, a DNA computation-mediated DNAzyme platform that can be activated by 808 nm NIR light and target c-MYC was designed for spatiotemporally controlled ultra -sensitive AND-gated molecular imaging. Particularly, the sensing and recognition function of the traditional DNAzyme platform was inhibited by introducing a blocking sequence containing a photo-cleavable linker (PC-linker) that can be indirectly cleaved by 808 nm NIR light and thus enables the AND-gated molecular imaging. According to the responses toward three designed SDz, nPC-SDz, and m-SDz DNAzyme probes, the fluorescence recovery in diverse cell lines (MCF-7, HeLa, and L02) and inhibitor-treated cells was investigated to confirm the AND-gated sensing mechanism. It is worth noting that thanks to the strand displacement amplification and the ability of gold nanopyramids (Au NBPs) to enhance fluorescence, the fluorescence intensity increased by similar to 7.9 times and the detection limit decreased by nearly 40.5 times. Moreover, false positive signals can be also excluded due to such AND-gated design. Furthermore, such a designed "AND-gate" sensing manner can also be applied to spatiotemporally controlled ultrasensitive in vivo molecular imaging, indicating its promising potential in precise biological molecular imaging.