A H2S-triggered two-photon ratiometric fluorescent theranostic prodrug for bio-imaging

We designed and synthesized a ratiometric fluorescent prodrug capable of releasing active therapeutic component while detecting hydrogen sulfide. Hydrogen sulfide (H 2 S) is a signaling molecule that plays important roles in biological systems. The exploration of H 2 S as a new drug release trigger and its related fluorescent theranostic system is crucial for cancer bio-imaging and therapy. Herein, we designed a new two-photon ratiometric fluorescent theranostic prodrug (compound 1 ) and studied its spectroscopic properties and application in in vivo imaging. Compound 1 specifically reacted with H 2 S and released the free active therapeutic component of 7-ethyl-10-hydroxycamptothecin, which was accompanied with a red-shift fluorescence emission signal from 460 nm to 545 nm. The exogenous and endogenous H 2 S in living cells were imaged by compound 1 under one-photon and two-photon excitation. Furthermore, compound 1 monitored the H 2 S concentration changes in Caenorhabditis elegans by fluorescence imaging. Additionally, it showed effective drug release activation in situ tumor with exogenous and endogenous H 2 S as the trigger. The H 2 S-sensitive activation and drug-release properties highlight the potential of theranostic compound 1 in future cancer treatment and therapy.