PT - JOURNAL ARTICLE AU - Xiong, Hejian AU - Alberto, Kevin A. AU - Youn, Jonghae AU - Taura, Jaume AU - Morstein, Johannes AU - Li, Xiuying AU - Wang, Yang AU - Trauner, Dirk AU - Slesinger, Paul A. AU - Nielsen, Steven O. AU - Qin, Zhenpeng TI - Optical Control of Neuronal Activities with Photoswitchable Nanovesicles AID - 10.1101/2022.06.10.495373 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.06.10.495373 4099 - http://biorxiv.org/content/early/2022/06/12/2022.06.10.495373.short 4100 - http://biorxiv.org/content/early/2022/06/12/2022.06.10.495373.full AB - Precise modulation of neuronal activity by neuroactive molecules is essential for understanding brain circuits and behavior. However, tools for highly controllable molecular release are lacking. Here, we developed a photoswitchable nanovesicle with azobenzene-containing phosphatidylcholine (azo-PC), coined ‘azosome’, for neuromodulation. Irradiation with 365 nm light triggers the trans-to-cis isomerization of azo-PC, resulting in a disordered lipid bilayer with decreased thickness and cargo release. Irradiation with 455 nm light induces reverse isomerization and switches the release off. Real-time fluorescence imaging shows controllable and repeatable cargo release within seconds (< 3 s). Importantly, we demonstrate that SKF-81297, a dopamine D1-receptor agonist, can be released from the azosome to activate cultures of primary striatal neurons. Azosome shows promise in precise optical control over the molecular release and can be a valuable tool for molecular neuroscience studies.Competing Interest StatementThe authors have declared no competing interest.