Photo-controllable biochemistry: Exploiting the photocages in phototherapeutic window

Photochemical tools have revolutionized the landscape of biomedicine, enabling the exploration of nature in a noninvasively remote-controlled manner. Among them, especially appealing is the photocage. Recently, significant breakthroughs in photocages have been achieved in drug delivery systems, optical-controlled protein degradation, and RNA modulation. However, existing photocages have mostly centered on excitation in the ultraviolet-visible range, which has limited penetration depth, thus hindering their practical applications. In contrast, deep red or NIR light within the “phototherapeutic window” (650–900 nm) has unique advantages, such as minimized side effects and superior deep-tissue penetration. Nevertheless, strategies to rationally design such photocages and their underlying photochemical mechanisms of action remain elusive. Here, we plan to provide a comprehensive overview of recent advances of photocages in the phototherapeutic window, including their design principles, photocaging performance, photoactivation mechanism, and emerging utilizations in biomedical chemistry. It is hoped that this review will inspire the future development of photocage-related research.