Activity-Triggered Chemiluminescent Probe for α-L-Fucosidase Detection from In Vitro to In Vivo

Area of Science:

• Biochemistry
• Oncology
• Biomedical Engineering

Background:

• Hepatocellular carcinoma (HCC) is a major global health concern with high mortality rates.
• Early detection and monitoring are crucial for improving HCC patient outcomes.
• Current diagnostic methods for HCC lack ideal sensitivity and specificity.

Purpose of the Study:

• To develop a novel chemiluminescent probe (AFU-CL) for sensitive and selective detection of alpha-L-fucosidase (AFU).
• To evaluate the probe's efficacy in visualizing AFU activity in HCC cells, tumors, and patient serum.
• To establish AFU-CL as a potential biomarker for early HCC diagnosis.

Main Methods:

• Development of a chemiluminescent probe (AFU-CL) targeting AFU.
• Assessment of probe sensitivity, selectivity, and signal-to-noise ratio.
• In vitro studies using cultured HCC cells (MHCC-97H) and normal hepatocytes (MIHA).
• In vivo imaging in HCC-bearing mouse models.
• Clinical validation using serum samples from HCC patients and healthy controls.

Main Results:

• AFU-CL demonstrated high sensitivity (LOD = 4.87 × 10⁻⁴ mU/mL) and selectivity for AFU.
• Real-time visualization of endogenous AFU activity in HCC cells, differentiating malignant from normal hepatocytes.
• Successful in situ visualization of tumor sites in mouse models.
• Reliable differentiation of serum samples between HCC patients and healthy individuals.

Conclusions:

• The AFU-CL probe is a sensitive and selective tool for AFU detection.
• AFU-CL enables effective visualization of AFU activity in cellular and in vivo models of HCC.
• This strategy holds significant promise for early HCC diagnosis and monitoring through AFU biomarker analysis.