An extrinsic enzyme-activatable fluorescent probe for high-contrast tumor imaging

Area of Science:

• Biomedical Imaging
• Chemical Biology
• Oncology

Background:

• Malignant tumors present significant health risks, necessitating accurate early diagnosis and complete surgical resection.
• Fluorescence imaging aids intraoperative navigation but faces limitations like photobleaching and low signal-to-noise ratios, impacting surgical accuracy.
• Current fluorescent probes can lead to false-negative or false-positive results, compromising treatment decisions.

Purpose of the Study:

• To develop a novel enzyme-activated fluorescent probe for enhanced tumor visualization.
• To improve the accuracy of intraoperative tumor detection and resection.
• To overcome the limitations of conventional fluorescent dyes in cancer imaging.

Main Methods:

• Development of a specific fluorescent probe, TMN-CPG, designed for activation by carboxypeptidase G2 (CPG2).
• Utilizing CPG2-mediated hydrolysis to release a highly fluorescent molecule (TMN-NH2) upon activation.
• Evaluating the probe's performance in a 4T1 tumor-bearing mouse model for high-contrast tumor imaging.

Main Results:

• The developed probe, TMN-CPG, demonstrated specific activation by CPG2, releasing a fluorescent product.
• The enzyme-activated fluorescence system successfully produced high-contrast tumor imaging in vivo.
• The probe's activation mechanism led to tumor-specific fluorescence and internalization by cancer cells.

Conclusions:

• The external enzyme-activatable probe significantly improves tumor imaging accuracy by minimizing nonspecific activation.
• This approach enhances the precision of surgical tumor resection and supports better treatment planning.
• The study highlights the potential of enzyme-activated probes for advanced cancer diagnostics and surgical guidance.