posted on 2023-01-06, 13:07authored byWenliang Wang, Xiang Wu, Kai Wing Kevin Tang, Ilya Pyatnitskiy, Rayna Taniguchi, Peter Lin, Richard Zhou, Sam Lander C. Capocyan, Guosong Hong, Huiliang Wang
Optogenetics has revolutionized neuroscience understanding
by allowing
spatiotemporal control over cell-type specific neurons in neural circuits.
However, the sluggish development of noninvasive photon delivery in
the brain has limited the clinical application of optogenetics. Focused
ultrasound (FUS)-derived mechanoluminescence has emerged as a promising
tool for in situ photon emission, but there is not yet a biocompatible
liquid-phase mechanoluminescence system for spatiotemporal optogenetics.
To achieve noninvasive optogenetics with a high temporal resolution
and desirable biocompatibility, we have developed liposome (Lipo@IR780/L012)
nanoparticles for FUS-triggered mechanoluminescence in brain photon
delivery. Synchronized and stable blue light emission was generated
in solution under FUS irradiation due to the cascade reactions in
liposomes. In vitro tests revealed that Lipo@IR780/L012 could be triggered
by FUS for light emission at different stimulation frequencies, resulting
in activation of opsin-expressing spiking HEK cells under the FUS
irradiation. In vivo optogenetic stimulation further demonstrated
that motor cortex neurons could be noninvasively and reversibly activated
under the repetitive FUS irradiation after intravenous injection of
lipid nanoparticles to achieve limb movements.