NIR-triggered photocatalytic decaging for remote-controlled spatiotemporal activation in living mice

Spatiotemporal manipulation of biological processes in living animals using non-invasive, remote-controlled stimuli is a captivating but challenging endeavor. Herein, we present the development of a bioorthogonal photocatalytic technology termed CAT-NIR, which uses external near infrared light (NIR, 740 nm) to trigger bioorthogonal chemical decaging reactions in living mice. The Os(tpy)2 complex was identified as an efficient NIR photocatalyst for promoting deboronative hydroxylation reactions in the presence of NIR lights, resulting in the deprotection of phenol groups and the release of bioactive molecules under bioorthogonal conditions. The validation of the CAT-NIR system was demonstrated through the NIR-triggered rescue of fluorophores, prodrugs as well as biomolecules ranging from amino acids, peptides to proteins in living cells. Furthermore, by combining genetic code expansion and computer-aided screening, CAT-NIR was able to regulate affibody binding to the cell surface receptor Her2 in living cells, providing a highly selective cell tagging technology with spatiotemporal precision through external NIR light. Most significantly, the tissue-penetrating ability of NIR light allowed for smooth prodrug activation in living mice using external NIR light, enabling non-invasive, remote-controlled rescue of bioactive molecules. This opens up new opportunities for in vivo investigations and manipulations given the broad adaptability of the decaging chemistry and the high spatiotemporal resolution potential of such photocatalytic tools.