Regulating the activity of specific neurons is essentially important in neurocircuit dissection and neuropathy therapy. As a recently developed strategy, nanomaterial-enabled non-genetic neuromodulations that realize remote physical stimuli have made vast progress and shown great clinical potential. However, minimal invasiveness and high spatiotemporal resolution are still challenging for non-genetic neuromodulation. Herein, we report a second near-infrared (NIR-II) light-induced transcranial non-genetic neurostimulation via bioinspired nano-vesicles. The rationally designed vesicles are obtained from vesicle membrane-confined enzymatic reactions. This study demonstrates that the vesicle-enabled NIR-II photothermal stimuli can elicit neuronal signaling dynamics with precise spatiotemporal control and thus evoke defined neural circuits in non-transgenic mice. Moreover, the vesicle-mediated NIR-II optical stimulation can regulate mouse motor behaviors with minimal invasiveness by eliminating light-emitting implants. Furthermore, the biological modulation is integrated with photoacoustic brain imaging, realizing navigational and efficient neuromodulation. Such transcranial and precise NIR-II optical neuromodulation mediated by bioinspired vesicles shows the potential for the optical-theranostics of neurological diseases in non-transgenic organisms. This article is protected by copyright. All rights reserved.
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