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Updated: May 9, 2026
A Bright NIR-II Fluorescence Probe for Vascular and Tumor Imaging
Published on: March 17, 2023
An extrinsic enzyme-activatable fluorescent probe for high-contrast tumor imaging
Yifang Guo1,2, Yuwei Du1,2, Liru Heng2
1School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China Hefei 230026 China.
Abstract:
Malignant tumors pose a major threat to human health, and the effectiveness of treatment largely depends on accurate early diagnosis and complete resection. Although fluorescence imaging offers high sensitivity and enables real-time visualization for intraoperative navigation, conventional fluorescent dyes are limited by photobleaching, poor targeting, and low signal-to-noise (S/N) ratios. These limitations result in false-negative or false-positive outcomes, thereby compromising the precision of surgery and the validity of subsequent treatment decisions. Herein, we developed a fluorescent probe, TMN-CPG, which is specifically activated by carboxypeptidase G2 (CPG2), an enzyme notable for prodrug activation in antibody-directed enzyme prodrug therapy (ADEPT). Upon CPG2-mediated hydrolysis of the TMN-CPG amide bond, the highly fluorescent TMN-NH2 is released and subsequently internalized by cancer cells, resulting in tumor-specific fluorescence. In a 4T1 tumor-bearing mouse model, this extrinsic enzyme-activated fluorescence system produced high-contrast tumor imaging. These results indicate that this external enzyme-activatable probe can minimize nonspecific activation, thereby improving the accuracy of tumor imaging.
Insights
A novel fluorescent probe, TMN-CPG, activated by carboxypeptidase G2 (CPG2), enhances tumor imaging accuracy. This enzyme-activated system minimizes false outcomes, improving surgical precision and treatment decisions for malignant tumors.
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.
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