Synergistic Photothermal‐Chemical Rescue of Single Injured Neuron via Optical Fiber‐Guided Nanomotors

Abstract

Precise neuromodulation for neural repair remains challenging because it requires both spatially confined stimulation and effective relief of local inhibitory signaling, which are difficult to achieve simultaneously. Here, we present an optical fiber‐guided metal–organic framework (MOF) nanomotor system that extends previous optical scattering‐force neuromodulation strategies by integrating localized photothermal stimulation with on‐demand therapeutic drug delivery for subcellular neural repair. Under 980 nm laser illumination delivered through a tapered optical fiber, forward‐scattering optical forces propel the nanomotors, allowing deterministic targeting of specific neuronal substructures such as the soma and axon. Simultaneously, the nanomotors generate localized photothermal heating sufficient for neuronal activation, as confirmed by transient receptor potential vanilloid 1 (TRPV1)‐dependent Ca 2+ influx and inward currents. Remarkably, the combination of nanomotor‐mediated photothermal and fasudil chemical stimulation synergistically restores axon growth of injured neurons to levels approaching those of intact neurons, with significantly improved efficiency compared with either single stimulation alone. By integrating biochemical disinhibition and physical stimulation within a single optically guided MOF nanomotor, this strategy provides new possibilities for localized neural repair and neuromodulation through precise subcellular targeting.