Peptide Receptor-Targeted Fluorescent Probe: Visualization and Discrimination between Chronic and Acute Ulcerative...

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Gastroenterology

Background:

• Inflammatory activity in ulcerative colitis (UC) is crucial for treatment, but noninvasive real-time monitoring remains challenging.
• Distinguishing between chronic and acute colitis noninvasively is difficult.
• Oligopeptide transporter (PepT1) is overexpressed in chronic UC colonic epithelial cells, acting as a receptor for tripeptide KPV.

Purpose of the Study:

• To develop a PepT1 receptor-targeted fluorescent probe for noninvasive imaging of colitis.
• To enable real-time monitoring and differentiation of colitis activity (chronic vs. acute).
• To provide an alternative to traditional invasive diagnostic methods like H&E staining.

Main Methods:

• Conjugation of tripeptide KPV to a dicyanomethylene-4H-pyran (DCM) chromophore to create the DCM-KPV fluorescent probe.
• Utilizing Caco-2 cells with overexpressed PepT1 to model chronic ulcerative colitis.
• Co-localization studies with DCM-KPV and DNA-specific fluorophore DAPI for cellular uptake and localization analysis.
• In vivo imaging via intestinal mucosa to observe probe accumulation in colon inflammation regions.

Main Results:

• The DCM-KPV probe exhibits specific receptor-targeted interaction with PepT1.
• The probe possesses beneficial characteristics: efficient long emission, low photobleaching, negligible cytotoxicity, and high cytocompatibility.
• DCM-KPV successfully achieved noninvasive observation and differentiation of chronic colitis, acute colitis, and normal groups via intestinal mucosa.
• The probe demonstrated superior sensing selectivity compared to unenhanced MRI and H&E staining.

Conclusions:

• The PepT1-targeted fluorescent probe DCM-KPV offers a breakthrough for direct, noninvasive visualization of colon inflammation.
• This method effectively distinguishes between chronic and acute ulcerative colitis.
• DCM-KPV provides a real-time, noninvasive alternative to conventional diagnostic techniques, improving colitis management.