Ultrasound Triggered Liposome Light Source for Noninvasive Optogenetics

Optogenetics has revolutionized neuroscience understanding by allowing spatiotemporal control over cell-type specific neurons in neural circuits. However, visible light cannot be directly delivered to deep brain tissue, due to the severe dissipation and scattering of photons. As a result, invasive craniotomy is usually required to implant optical fibers in the brain for in vivo optogenetic stimulation, resulting in permanent damage and chronic gliosis in brain tissue. To achieve non-invasive optogenetics with high temporal resolution and excellent biocompatibility, we have developed focused ultrasound triggered liposome-based light sources (Lipo@IR780/L012 nanoparticles) for deep brain photon delivery. Synchronized and stable blue light emission was generated under ultrasound irradiation due to the activation of chemiluminescent L012 via nearby reactive oxygen species generated by IR780. In vitro tests revealed that Lipo@IR780/L012 nanoparticles could be triggered by ultrasound for light emission at different frequencies and hence activate opsin-expressing spiking HEK cells under the ultrasound irradiation. In vivo optogenetic stimulation further demonstrated that motor cortex neurons could be noninvasively and reversibly activated under the repetitive ultrasound stimulation after i.v. injection of Lipo@IR780/L012 nanoparticles to achieve limb motions control.