Subcellular Concurrent Delivery of Hydrogen Sulfide and A Payload with Near-Infrared Light

Hydrogen sulfide (H2S) is a gaseous signaling molecule, exerting crucial regulatory functions in organelles and cellular environments. H2S exhibits high therapeutic potential, synergistic effects with other drugs, and its potency is notably enhanced through organelle-specific targeting. Yet navigation of light-activated H2S donors to specific organelles remains absent. Here we report a cyanine-based dual-action photocage operated by tissue-penetrating near-infrared light. The system simultaneously delivers H2S and a fluorogenic payload, displaying a self-reporting behavior of the uncaging. We demonstrate that H2S and an amine payload are concurrently uncaged in the mitochondria of live human cells using fluorescence microscopy and confirm the localization of their delivery using mitochondria-specific fluorescent probes. Anticipating that these photocages will permit the future delivery of H2S–drug pairs with high spatiotemporal control, we envision these photocages to drive harnessing synergistic effects and opening the way to innovative therapeutic avenues.