Near‐Infrared‐Light Activatable Nanoparticles for Deep‐Tissue‐Penetrating Wireless Optogenetics

Abstract Optogenetics has been developed to control the activities and functions of cells with high spatiotemporal resolution, cell‐type specificity, and flexibility. However, current optogenetic tools generally rely on visible light (e.g., blue or yellow) with shallow tissue penetration ability that does require invasive fiber‐optic probes to deliver visible light into organs and animal tissues. This often results in a series of side effects, such as tissue damage and unwanted inflammation. Fortunately, the emerging wireless optogenetic tools that can respond to deep‐tissue‐penetrating near‐infrared (NIR) light have attracted increasing attention due to their much‐reduced damage to living organisms. There are mainly two types of NIR‐activatable optogenetic tools: one uses lanthanide‐doped upconversion nanoparticles to transduce NIR light to visible light to modulate classical opsin‐expressing neurons; the other type couples with an NIR absorber to convert NIR light to heat to activate thermosensitive proteins. These NIR‐activatable optogenetic tools enable low‐invasive “remote control” activation and inhibition of cellular signaling pathways. This approach has great potential to help create more innovative therapies for diseases like cancer, diabetes, and neuronal disorders in the near future. Therefore, this review article summarizes the recent advances on design strategies and synthetic methods of NIR‐activatable nanomaterials for wireless optogenetic applications.