Mechanoluminescent HOF Nanotransducers Enabled Sono‐Optogenetics in Parkinsonian Rats

ABSTRACT Ultrasound‐triggered mechanoluminescence has emerged as a promising strategy for non‐invasive light delivery, enabling remote neuromodulation that advances optogenetics and accelerates its clinical translation. However, existing mechanoluminescent nanotransducers lack sufficient brightness and durable, repeatable emission to effectively modulate brain function in deep regions for potential treatment of neurodegenerative diseases. Here, we report sonosensitized hydrogen‐bonded organic frameworks (HOFs), which function as nanoscale light delivery system activated by ultrasound stimulation. These nanotransducers achieve high brightness and prolonged, repeatable emission, enabling precise neural modulation across multiple brain regions. Using these nanotransducers, we demonstrate effective motor cortex modulation for limb control in mice and selective activation of parvalbumin (PV)‐expressing neurons in the external globus pallidus (GPe), rescuing motor dysfunction in dopamine‐depleted Parkinson's disease rats. This work establishes a pathway toward genetically targeted, non‐invasive neuromodulation for Parkinson's disease, with potential translation to non‐human primates and clinical settings. Beyond neuromodulation, this technology represents a versatile tool for non‐invasive monitoring and control of light‐responsive cellular processes.