Early Ferroptosis Detection Targeting Lipid Hydrogen Abstraction

Area of Science:

• Biochemistry
• Cell Biology
• Chemical Biology

Background:

• Ferroptosis is a regulated cell death pathway driven by iron-dependent lipid peroxidation.
• Early detection of ferroptosis is crucial for effective diagnosis and treatment.
• Lipid hydrogen abstraction initiates the ferroptosis cascade, making it a key target for early detection.

Purpose of the Study:

• To develop novel fluorogenic probes for the specific detection of lipid hydrogen abstraction.
• To enable earlier and more sensitive detection of ferroptosis.
• To facilitate mechanistic studies of ferroptosis.

Main Methods:

• Design and synthesis of three fluorogenic probes: LHA585 (red), LHA675 (deep-red), and LHA930 (near-infrared).
• Utilized a 4-phenyl-3-methylbut-2-enyl moiety as a lipid mimic to detect oxidative radicals.
• Evaluated probe performance in vitro (OGD/R model) and in vivo.

Main Results:

• The LHA probes specifically detect lipid hydrogen abstraction, the initiating event in ferroptosis.
• LHA585 demonstrated an ~8-hour earlier fluorescence turn-on than the gold standard in an in vitro model.
• LHA930 proved effective for in vivo ferroptosis detection.

Conclusions:

• The LHA probes represent a significant advancement in ferroptosis sensing technology.
• These probes enable earlier and more precise detection of ferroptosis.
• The LHA probes are valuable tools for investigating lipid-peroxidation-driven cell death.