Spatiotemporal neuromodulation via reversible and photothermal-gated DNA nanochannels

<h2>Summary</h2> 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 <i>in vivo</i>. 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-Fe₃O₄ 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_V1.7-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 <i>in vivo</i> neuromodulation.