Intelligent Programmable DNA Nanomachines for the Spatially Controllable Imaging of Intracellular MicroRNA

The high programmability of DNA molecules makes them particularly suitable for constructing artificial molecular machines to perform sophisticated functions by simulating complex living systems. However, intelligent DNA nanomachines which can perform precise tasks logically in complex environments still remain challenging. Herein, we develop a general strategy to design a pH-responsive programmable DNA (PRPD) nanomachine to perform multilayer DNA cascades, enabling precise sensing and calculation of intracellular biomolecules. The PRPD nanomachine is built on a four-stranded DNAzyme walker precursor with a DNA switch on the surface of an Au nanoparticle, which is capable of precisely responding to pH variations in living cells by sequence tuning. This multilayer DNA cascade networks have been applicated in spatially controlled imaging of intracellular microRNA, which efficiently avoided the DNA nanomachine activated by nonspecific extracellular molecules and achieved apparent signal amplification. Our strategy enables the sensing-computing-output functional integration of DNA nanomachines, facilitating the application of programmable and complex nanomachines in nanoengineering, chemistry, and biomedicine.