Dual-Locked Fluorescent Probes Activated by Aminopeptidase N and the Tumor Redox Environment for High-Precision Imaging of Tumor Boundaries

Yang Shen ¹, Wei Li ^1,2, Zhixuan Zhou ¹

⁰State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, P. R. China.

Angewandte Chemie (International Ed. in English) +

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May 23, 2024

View abstract on PubMed

Summary

This study introduces a novel fluorescent probe strategy for precise tumor margin imaging. The developed probe accurately distinguishes tumor from healthy tissue, improving surgical resection and reducing recurrence.

Area Of Science

Biomedical Engineering
Oncology
Medical Imaging

Background

Accurate tumor margin delineation is critical for effective surgical resection and reducing cancer recurrence.
Current fluorescence imaging probes often lack the specificity required for precise tumor boundary identification.
Limitations in traditional methods necessitate the development of advanced imaging agents for intraoperative guidance.

Purpose Of The Study

To design and develop activatable fluorescent probes for high-precision imaging of tumor boundaries.
To address the limitations of traditional probes by integrating multi-dimensional tumor characteristics.
To improve intraoperative diagnosis and surgical resection of tumors.

Main Methods

An offensive and defensive integration (ODI) strategy was employed, targeting tumor-specific "attack" (invasive peptidase) and "defense" (reductive microenvironment) systems.
Fluorescent probes, including ANQ and derivatized FANQ, were designed and screened based on the ODI strategy.
In vivo and ex vivo imaging experiments were conducted using mouse models and clinical samples of hepatocellular carcinoma.

Main Results

The ODI strategy-based probe ANQ demonstrated superior performance over traditional probes in distinguishing tumor cells from normal cells and minimizing false positives.
Derivatized FANQ significantly improved the signal-to-background ratio for in vivo imaging.
Successful differentiation of orthotopic hepatocellular carcinoma tissues from adjacent normal tissues was achieved in both animal models and clinical samples.

Conclusions

The developed activatable fluorescent probes, based on the innovative ODI strategy, enable precise imaging of tumor boundaries.
This approach offers a significant advancement for rapid tumor diagnosis and intraoperative assisted resection.
The findings provide more effective tools for clinical applications in cancer surgery.

Keywords:

activatable fluorescent probe high-precision imaging molecular imaging orthotopic hepatocellular carcinoma tumor boundary

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