A Membrane-Impermeable Near-Infrared Probe Enables High-Fidelity Tracking of Foam Cell Progression.

Area of Science:

• Biomedical Imaging
• Molecular Biology
• Cardiovascular Research

Background:

• Foam cell formation is a critical process in atherosclerosis development.
• Existing methods struggle to differentiate pathological lipid aggregates in foam cells from normal lipid droplets in live cells.
• Accurate imaging of foam cells is crucial for early diagnosis and targeted drug development in atherosclerotic disease.

Purpose of the Study:

• To develop a novel fluorescent probe for high-fidelity, live-cell imaging of foam cell formation.
• To overcome limitations of current methods in distinguishing pathological from normal lipid accumulation.
• To enable rapid and dynamic monitoring of lipid accumulation in foam cells.

Main Methods:

• Synthesis of a membrane-impermeable, near-infrared fluorescent probe (FMNIR-DBO) with a charged, rigid moiety.
• Utilizing the loss of plasma membrane integrity during foam cell transformation for selective probe entry.
• Live-cell imaging of foam cell formation and lipid accumulation.

Main Results:

• FMNIR-DBO selectively enters foam cells by exploiting compromised plasma membrane integrity, illuminating pathological lipid aggregates.
• The probe effectively distinguishes pathological lipid aggregates from normal lipid droplets in live cells, eliminating interference.
• Rapid, dynamic imaging of lipid accumulation in foam cells was achieved within 6 hours, significantly faster than conventional Oil Red O staining.
• The probe was successfully used to evaluate ethanol's effects on foam cell formation, supporting its role in alcohol-induced atherosclerosis.

Conclusions:

• FMNIR-DBO provides a powerful tool for high-fidelity, real-time imaging of foam cell formation.
• This probe facilitates early diagnosis and drug screening for atherosclerotic diseases.
• The developed strategy offers a significant advancement in understanding and potentially treating atherosclerosis.