Ligand‐Directed H₂S Probe and Scavenger for Specific Tumor Imaging

Abstract An expanding body of evidence suggests that specifically targeting hydrogen sulfide (H 2 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 H 2 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 H 2 S at 803 nm with high specificity. PSMA‐Py‐NBD can scavenge H 2 S fast ( k 2 =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 H 2 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 H 2 S cancer biology and with related therapies.