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

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Cancer Therapeutics

Background:

• Hydrogen sulfide (H2S) shows potential in cancer diagnosis and treatment.
• A need exists for targeted molecular tools for in vivo H2S detection and modulation in cancer.

Purpose of the Study:

• To develop and evaluate novel H2S-specific near-infrared fluorescent sensors and scavengers targeting the prostate-specific membrane antigen (PSMA).
• To assess the efficacy of these tools in PSMA-expressing prostate cancer cells and in vivo tumor models.

Main Methods:

• Synthesis of PSMA-targeted H2S sensor (PSMA-Cy7-NBD) and scavenger (PSMA-Py-NBD).
• Evaluation of sensor specificity, fluorescence response, and scavenger kinetics.
• Cellular uptake studies in PSMA-expressing prostate cancer cells.
• In vivo imaging and H2S downregulation in murine 22Rv1 tumor models.

Main Results:

• PSMA-Cy7-NBD demonstrated a 53-fold off-on fluorescence response to H2S with high specificity.
• PSMA-Py-NBD efficiently scavenged H2S without interfering with biothiols.
• Both agents were selectively transported into PSMA-positive cancer cells.
• In vivo imaging and downregulation of endogenous H2S levels were achieved in tumor models.

Conclusions:

• The developed PSMA-targeted tools offer a promising approach for H2S-specific imaging and therapy in prostate cancer.
• These molecular tools can facilitate further investigation into H2S-mediated cancer biology and therapeutic strategies.