Based on thiolysis of the NBD amine, a H<sub>2</sub>S-triggered prodrug has been designed and synthesized for localized production of ciprofloxacin under micromolar H<sub>2</sub>S. Activation of the prodrug can be monitored through fluorescence in real-time. We envision that thiolysis of the NBD amine could be readily used for development of other H<sub>2</sub>S-triggered prodrugs in the future.