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Toward non-genetic non-invasive neural modulation with a submillimeter precision, we report the development and application of photoacoustic nanotransducers (PAN) to neural stimulation in cultured primary neurons and in live brain. Our PAN, based on synthesized semiconducting polymer nanoparticles, efficiently generate localized ultrasound by a photoacoustic process upon absorption of nanosecond pulsed light in the NIR-II window. We showed that PAN binding on the neuron membrane through non-specific interaction and specific targeting of mechanosensitive ion channels both successfully activate primary neurons in culture. We also demonstrated in live mouse brain motor cortex activation and invoked subsequent motor responses through PAN.
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