Two-photon fluorescence probe for precisely detecting endogenous H2S in lysosome by employing a dual lock system

Hydrogen sulfide (H2S) is involved in various pathological and physiological processes as well as regulation of lysosomal functions. Thus, it is essential to develop precise method for the detection of H2S in lysosome. Although a large number of fluorescent probes for H2S have been developed, the probe for lysosomal H2S assay still remains rare. Herein, a two-photon fluorescent probe, named Lyso-Nap, is designed and synthesized for detecting H2S in lysosome by employing a dual lock system (dual PET process and dual reaction sites). The fluorescence of Lyso-Nap with dual lock system is opened by H2S only when the probe is localized within acidic lososomes, which can avoid the disturbance from neutral cytosol and other organelles. Moreover, two-photon fluorescent probes with weak auto-fluorescence, large penetration depth and reduced photodamage, are particularly favored for bioimaging. Accordingly, Lyso-Nap can be successfully used for precisely tracking and detecting endogenous H2S in lysosome of living cells and tissue.