Spatiotemporal neuromodulation via reversible and photothermal-gated DNA nanochannels

Dynamically modulating neurons at the molecular scale is essential to precisely treat neurological disorders, yet current approaches face the dilemma of achieving high spatiotemporal resolution or genetic editing issues in vivo . Here, we report a non-genetic neuromodulation strategy leveraging reversible and photothermal-gated DNA nanochannels to achieve nanoscale-spatial resolution and second-level temporal control. This system integrates thermo-responsive DNA nanochannels with Au-Fe 3 O 4 Janus nanoparticles as the localized near-infrared (NIR) photothermal converters, enabling 98.4% cellular membranes insertion and reversible conformational changes of DNA nanochannels to regulate neurons. Upon periodic 808-nm laser irradiation, the nanochannels exhibit cyclical gating of ion transport, enhancing the excitability of dorsal root ganglion neurons within seconds. The strategy restores pain sensation in the Na V 1.7-KO mice upon 1-min laser irradiation. By synergizing DNA nanotechnology with NIR photothermal actuation, these artificial nanochannels overcome the spatiotemporal trade-off of conventional tools with control accuracy, offering a versatile strategy for in vivo neuromodulation.