Near-Infrared Ratiometric Fluorescent Probe for Monitoring Hypochlorous Acid in Ferroptosis Models

Area of Science:

• Biochemistry
• Cell Biology
• Medical Imaging

Background:

• Ferroptosis is a regulated cell death pathway linked to oxidative stress.
• Hypochlorous acid (HClO) levels correlate with ferroptosis onset and progression.
• Understanding the HClO-ferroptosis relationship is crucial for disease research.

Purpose of the Study:

• To develop a near-infrared (NIR) ratiometric fluorescent probe for imaging HClO variations.
• To investigate the role of HClO in ferroptosis models.
• To provide a tool for monitoring HClO in ferroptosis-related diseases.

Main Methods:

• Synthesis of a novel NIR ratiometric fluorescent probe (BV-HD) based on phenothiazine oxidation.
• Detection of exogenous and endogenous HClO concentrations in cells using ratiometric fluorescence.
• Monitoring HClO levels in Erastin-induced ferroptosis models and drug-induced liver injury mice.

Main Results:

• The BV-HD probe successfully imaged HClO variations in ferroptosis models.
• Up-regulated HClO fluxes were observed in Erastin-induced ferroptosis cells.
• HClO levels were significantly reduced by ferroptosis inhibitors (ferrostatin-1, glutathione, N-acetylcysteine).
• Elevated HClO was detected in drug-induced liver injury and ferroptosis mouse models.

Conclusions:

• The developed NIR ratiometric fluorescent probe (BV-HD) is effective for monitoring HClO concentrations.
• This method aids in uncovering biological mechanisms underlying ferroptosis.
• The probe offers a valuable tool for studying ferroptosis-related diseases.