Ratiometric Detection of Carboxylesterase In Vitro and In Vivo via a BODIPY-Styryl Platform

Area of Science:

• Biochemistry
• Medical Diagnostics
• Chemical Biology

Background:

• Hepatocellular carcinoma (HCC) is a deadly liver cancer with limited early diagnostic tools.
• Carboxylesterase (CE) is a potential biomarker for HCC due to its abundance in liver tissue.

Purpose of the Study:

• To develop a novel fluorescent probe for sensitive and specific detection of CE.
• To enable ratiometric detection and imaging of CE for distinguishing cancerous from normal liver cells.

Main Methods:

• Design and synthesis of a BODIPY-styryl based fluorescent probe (BDPPh-CES).
• In vitro testing for specificity against other enzymes and performance at physiological pH.
• Mechanistic studies using HRMS, DFT, and molecular docking.
• Cellular imaging in Hepa 1-6 (cancer) and AML 12 (normal) cells.
• In vivo validation for liver-specific accumulation and CE detection.

Main Results:

• BDPPh-CES exhibits ratiometric detection of CE with a red-shifted emission within 30 minutes.
• The probe shows high specificity for CE over AChE and stability across physiological pH.
• Successful real-time ratiometric imaging of elevated CE in HCC cells compared to normal cells.
• In vivo studies confirm liver-specific accumulation and effective CE detection.

Conclusions:

• BDPPh-CES is a sensitive and specific fluorescent probe for ratiometric CE detection.
• This probe facilitates cellular and in vivo imaging of CE, aiding in HCC diagnosis.
• The developed probe offers a promising tool for early detection and management of CE-related diseases like HCC.