Ligand-Directed H₂ S Probe and Scavenger for Specific Tumor Imaging

An expanding body of evidence suggests that specifically targeting hydrogen sulfide (H₂ S) might potentially benefit both tumor diagnosis and treatment, but there is still a lack of cancer-targeted molecular tools for in vivo applications. Here, we report the first ligand-directed H₂ S-specific near-infrared fluorescent sensor PSMA-Cy7-NBD and scavenger PSMA-Py-NBD that target the prostate-specific membrane antigen (PSMA). PSMA-Cy7-NBD displays a 53-fold off-on fluorescence response to H₂ S at 803 nm with high specificity. PSMA-Py-NBD can scavenge H₂ S fast (k₂ =30.8 M^-1  s^-1 at 25 °C) without interference from biothiols. Both tools are highly water-soluble and can be transported selectively into PSMA-expressing prostate cancer cells. Endogenous H₂ S levels in murine 22Rv1 tumor models can be imaged and downregulated by intravenous injection of PSMA-Cy7-NBD and PSMA-Py-NBD, respectively. These tools could potentially help to investigate H₂ S cancer biology and with related therapies.