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

Abstract 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.