DOTAM-Based, Targeted, Activatable Fluorescent Probes for the Highly Sensitive and Selective Detection of Cancer...

Area of Science:

• Molecular Imaging
• Biochemistry
• Oncology

Background:

• Cysteine proteases, such as cathepsin S, are implicated in tumor development and progression, serving as potential cancer markers.
• Combining substrate-based activatable probes with cellular targeting strategies for small-molecule cancer imaging is an underexplored area.

Purpose of the Study:

• To develop and evaluate a dual-functional, activatable, RGD-targeted fluorescent probe for cathepsin S-activated cancer imaging.
• To assess the probe's performance in vitro and in human cancer cell lines, comparing it to a non-targeted analog.

Main Methods:

• Design and synthesis of a dual-functional DOTAM-based, RGD-targeted, internally quenched fluorescent probe activated by cathepsin S.
• Evaluation of in vitro activation kinetics and cellular uptake in human cancer cell lines with varying integrin expression levels.
• Comparison of fluorescence staining intensity between the targeted, activatable probe and its non-targeted counterpart.

Main Results:

• The developed probe demonstrated excellent in vitro activation kinetics, which translated effectively to human cancer cell lines.
• The targeted, activatable probe showed superior uptake and significantly higher fluorescence staining in alpha-v-beta-3 integrin-expressing human sarcoma cells (HT1080) compared to the non-targeted probe.
• Profound probe activation was observed in cancer cells with lower integrin expression, while healthy cells exhibited minimal activation, indicating high cancer cell selectivity.

Conclusions:

• The dual-functionality concept, integrating a substrate-based activatable probe with a targeting approach, shows significant promise for cancer imaging.
• This novel probe design offers high sensitivity and selectivity, demonstrating potential for the development of advanced in vivo imaging agents for cancer detection.