Ligand‐Directed H2S Probe and Scavenger for Specific Tumor Imaging

An expanding body of evidence suggests that specifically targeting hydrogen sulfide (H2S) 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 H2S‐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 H2S at 803 nm with high specificity. PSMA‐Py‐NBD can scavenge H2S 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 H2S 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 H2S cancer biology and with related therapies. Sulfide scavenger: Molecular engineering of ligand‐directed H2S‐responsive tools yields a near‐infrared fluorescent probe and a scavenger for specifically imaging and downregulating the intratumoral H2S levels in live mice; this could potentially help to investigate H2S cancer biology and with related therapies.