Recent Progress in Azobenzene‐Based In Vivo Photopharmacology

As the most extensively studied photoswitch in photopharmacology, the azobenzene photoswitch has precision instrumental in the photoregulation of physiological processes across various animal models. Currently, it exhibits the greatest clinical potential for photosensitive retinal restoration, capable of inducing long-term therapeutic effects following intravitreal injection, without the need for foreign gene expression or optical fiber implantation. A significant advancement in the application of azobenzene photoswitches is their integration with optical flow control technology, which facilitates the targeting of deep tissues within the mouse cerebral cortex, addressing long-standing challenges related to tissue penetration depth in photopharmacology. With exceptional spatial and temporal resolution, photopharmacology is particularly well-suited for precision medicine, holding substantial potential for further development. Consequently, a comprehensive summary and review of the design strategies of azobenzene photoswitches for In Vivo applications, along with their experimental outcomes, are essential for guiding future advancements in photopharmacology. This review provides an overview of the fundamental properties and design strategies of azobenzene photoswitch molecules. Additionally, we extensively summarize all azobenzene photoswitch molecules successfully applied In Vivo for photopharmacological purposes since 2006, covering species such as Caenorhabditis elegans, Xenopus tadpoles, zebrafish, mice, rats, rabbits, and canines. Finally, we discuss the challenges associated with the In Vivo implementation of azobenzene photoswitch molecules and propose potential solutions.