Conditionally Activatable Photoredox Catalysis in Living Systems

Abstract

The transformational effect of photoredox catalytic chemistries has inspired new opportunities, enabling us to interrogate nature in ways that are not possible otherwise and to unveil new biotechnologies in therapy and diagnosis. However, the deployment of artificial photoredox catalysis in living systems remains challenging, mired by the off-target risk and safety concerns of photocatalyst toxicity. Here, we present an appealing approach, namely conditionally activatable photoredox catalysis (ConAPC), and as a proof of concept design the first ConAPC architecture (Se-NO₂) based upon classic self-immolative chemistry, in which the inherent photocatalytic properties can be temporarily caged while the species becomes active only at the tumor sites via sensing to specific biomarkers. Such a masking strategy allows a spatial-temporal control of photoresponsivity in vitro and in vivo. In particular, for ConAPC design, a new biologically benign metal-free photocatalyst (Se-NH₂), which is able to initiate NIR photoredox catalysis to manipulate the cellular electron pool in an O₂-independent mechanism of action, is identified. With this unique strategy, potent tumor-specific targeting photocatalytic eradication (TGI: 95%) is obtained in a mouse model. Impressively, favorable features such as high-resolution tumor recognition (SBR: 33.6) and excellent biocompatibility and safety are also achieved. This work therefore offers a new possibility for chemists to leverage artificial photocatalytic reactions toward the development of facile and intelligent photocatalytic theranostics.