Photothermal Modulation of Depression-Related Ion Channel Function through Conjugated Polymer Nanoparticles

Considering recent breakthroughs in the field of optogenetics, a powerful tool is established in the present study to modulate the activities of target neurons through the application of light-based methods. Near-infrared (NIR) light enables the penetration of deep-tissue. As a result, it can be used to modulate the functions of proteins/cells. Herein, it is aimed to develop a NIR light-sensitive drug delivery system to spatially and temporally control the activation of the loaded drug at the stimulation sites through its release from a nanoparticle sensitive to NIR. Owing to their excellent photothermal effect under NIR irradiation, the nanoparticles are found to penetrate the blood-brain barrier effectively, ultimately reaching neurons. Furthermore, by loading fasudil, a selective activator of the Kv7.4 potassium channel, into the precisely designed and synthesized NIR light-sensitive nanoparticles, the firing frequency of dopaminergic neurons in the ventral tegmental area is found to be remarkably reduced upon NIR light irradiation. Such findings shed light on a new concept that can be used for developing more selective drug therapies for the treatment of diseases, such as major depression.