Near‐Infrared Light Triggered‐Release in Deep Brain Regions Using Ultra‐photosensitive Nanovesicles

Remote and minimally‐invasive modulation of biological systems with light has transformed modern biology and neuroscience. However, light absorption and scattering significantly prevents penetration to deep brain regions. Herein, we describe the use of gold‐coated mechanoresponsive nanovesicles, which consist of liposomes made from the artificial phospholipid Rad‐PC‐Rad as a tool for the delivery of bioactive molecules into brain tissue. Near‐infrared picosecond laser pulses activated the gold‐coating on the surface of nanovesicles, creating nanomechanical stress and leading to near‐complete vesicle cargo release in sub‐seconds. Compared to natural phospholipid liposomes, the photo‐release was possible at 40 times lower laser energy. This high photosensitivity enables photorelease of molecules down to a depth of 4 mm in mouse brain. This promising tool provides a versatile platform to optically release functional molecules to modulate brain circuits. Ultra‐photosensitive nanovesicles are developed by coating gold shell on the surface of mechanoresponsive nanovesicles. Gold shell transduces near‐infrared laser pulses to nanomechanical force, leading to efficent cargo release in sub‐seconds. This high photosensitivity enables photorelease of molecules down to a depth of 4 mm in mouse brain.