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Dual Enzyme-Locked Activation Reporter for Accurate Liver Cancer Surveillance.
Yu-Jin Chen1,2, Hong Zhang1, Fei-Fan Xiang2
1Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.
Analytical Chemistry
|July 9, 2024
Summary
A new dual-locked probe, Si-NTR-LAP, enhances liver cancer detection by targeting two biomarkers, nitroreductase and leucine aminopeptidase. This improves tumor recognition and signal accuracy for better diagnosis and surgical guidance.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Cancer Diagnostics
Background:
- Accurate liver cancer monitoring requires activatable probes with high signal-to-background ratios.
- Single-biomarker probes risk misdiagnosis due to insufficient signal-to-noise ratios.
- Dual-biomarker strategies are needed for improved cancer surveillance.
Purpose of the Study:
- To develop and evaluate a dual-locked activation response probe (Si-NTR-LAP) for enhanced liver cancer detection.
- To assess the probe's performance against single-locked probes (Si-LAP, Si-NTR).
- To validate the probe's efficacy in preclinical liver cancer models.
Main Methods:
- Design of a dual-locked probe, Si-NTR-LAP, targeting nitroreductase and leucine aminopeptidase.
- Comparison of Si-NTR-LAP with single-locked probes (Si-LAP, Si-NTR) in vitro and in vivo.
- Evaluation in subcutaneous tumor and orthotopic hepatocellular carcinoma models.
Main Results:
- Si-NTR-LAP demonstrated superior tumor recognition compared to single-locked probes.
- The dual-locked probe achieved a significantly higher signal-to-noise ratio.
- Accurate identification of tumor tissue and differentiation from normal tissue was achieved in complex models.
Conclusions:
- The dual-locked probe Si-NTR-LAP offers improved specificity and accuracy for liver cancer detection.
- This probe provides a practical strategy for enhancing intraoperative fluorescence navigation.
- Dual-locked probes represent a promising advancement for clinical cancer surveillance and diagnosis.

