RT Journal Article SR Electronic T1 Optical Control of Neuronal Activities with Photoswitchable Nanovesicles JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.06.10.495373 DO 10.1101/2022.06.10.495373 A1 Xiong, Hejian A1 Alberto, Kevin A. A1 Youn, Jonghae A1 Taura, Jaume A1 Morstein, Johannes A1 Li, Xiuying A1 Wang, Yang A1 Trauner, Dirk A1 Slesinger, Paul A. A1 Nielsen, Steven O. A1 Qin, Zhenpeng YR 2022 UL http://biorxiv.org/content/early/2022/06/12/2022.06.10.495373.abstract 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.