An "AND" Logic Gated Near-Infrared Fluorescent Probe Simultaneously Sensing Superoxide Anion and Viscosity Enables...

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Cardiovascular Research

Background:

• Early atherosclerosis involves macrophage lipid uptake and oxidative stress, creating a complex microenvironment.
• Real-time monitoring of molecular events in early atherosclerotic lesions remains a significant challenge.
• Developing sensitive diagnostic strategies requires precise tracking of disease initiation.

Purpose of the Study:

• To develop a near-infrared (NIR) dual-locked fluorescent probe for simultaneous monitoring of superoxide anion (O2•−) and viscosity.
• To validate the probe's ability to specifically detect the "dual dysregulation" microenvironment characteristic of early atherosclerosis.
• To assess the probe's efficacy in tracking atherosclerotic plaque progression and enabling early diagnosis.

Main Methods:

• Construction of a novel NIR dual-locked fluorescent probe, PLAQ-SCAN.
• PLAQ-SCAN activation relies on the co-occurrence of both superoxide anion and increased viscosity.
• In vitro and in vivo evaluation of PLAQ-SCAN for monitoring macrophage foam formation and aortic plaque progression in a mouse model.

Main Results:

• PLAQ-SCAN demonstrated fluorescence turn-on only in the presence of both superoxide anion and viscosity changes, matching early AS microenvironment.
• The probe successfully monitored the dysregulation of O2•− and viscosity during macrophage foam cell formation.
• PLAQ-SCAN detected atherosclerotic plaque progression and serum signal changes by week 8, preceding conventional histopathology.

Conclusions:

• PLAQ-SCAN provides a powerful platform for real-time monitoring of O2•− and viscosity during atherosclerosis pathogenesis.
• This probe enables early atherosclerosis monitoring by precisely matching the dual dysregulation of early disease stages.
• PLAQ-SCAN facilitates synergistic mechanistic exploration and improved diagnostic capabilities for cardiovascular diseases.