A Bioluminescent Probe for H₂S Detection in Tumor Microenvironment

Area of Science:

• Biochemistry
• Molecular Biology
• Medical Imaging

Background:

• Hydrogen sulfide (H2S) is a key signaling molecule implicated in various diseases, including renal cell carcinoma (RCC).
• Current H2S detection methods for RCC lack sensitivity and often require artificial stimulation, limiting their in vivo applicability.
• There is a need for specific, sensitive probes for real-time H2S monitoring in RCC progression.

Purpose of the Study:

• To develop a novel H2S-sensitive bioluminescent probe for detecting and monitoring H2S in renal cell carcinoma.
• To evaluate the probe's sensitivity, selectivity, and efficacy in cancer cells and an in vivo RCC model.

Main Methods:

• Design and synthesis of a "caged" luciferin substrate (QTZ) functionalized with H2S recognition groups, creating the QTZ-N3 probe.
• Assessment of probe sensitivity and selectivity using biochemical assays.
• Validation of QTZ-N3 for endogenous H2S detection in 786-O-Nluc RCC cells and an RCC xenograft nude mouse model.

Main Results:

• The QTZ-N3 probe demonstrated good sensitivity (∼0.19 μM) and selectivity for H2S.
• QTZ-N3 successfully detected endogenous H2S in RCC cells without external stimuli.
• Real-time monitoring of H2S levels was achieved in an RCC xenograft nude mouse model, correlating with tumor progression.

Conclusions:

• QTZ-N3 is a sensitive and selective bioluminescent probe for H2S detection in RCC.
• The probe facilitates real-time, in vivo monitoring of H2S during RCC progression without artificial stimulation.
• This work provides a valuable tool for understanding H2S roles in RCC and developing new diagnostic strategies.