Cholesterol-Anchored AND-Logic NIR-II Probe for Triple-Responsive Atherosclerosis Imaging

Area of Science:

• Biomedical Imaging
• Molecular Probes
• Cardiovascular Research

Background:

• Early detection of atherosclerosis (AS) is vital for preventing cardiovascular events.
• Current imaging techniques lack sensitivity for early atherosclerotic plaques and microenvironmental risk biomarkers.
• Need for advanced molecular tools to simultaneously assess plaque vulnerability and lipid metabolism.

Purpose of the Study:

• To develop a novel near-infrared-II (NIR-II) probe, NKH-CHOL, for sensitive early detection of atherosclerosis.
• To synchronously target lipid-rich microenvironments and sense plaque vulnerability biomarkers.
• To enable simultaneous visualization of lipid metabolism disorders and oxidative stress in AS.

Main Methods:

• Development of NKH-CHOL, a cholesterol-anchored NIR-II probe with an AND-logic response.
• Leveraging cholesterol anchoring for precise localization and detecting viscosity/polarity shifts.
• Sensing hypochlorous acid (HClO) overexpression via myeloperoxidase activity.
• Utilizing a D-π-A structured fluorophore for signal activation under specific conditions.

Main Results:

• NKH-CHOL achieved high-contrast arterial plaque imaging in AS murine models.
• The probe demonstrated AND-logic response, activating only when viscosity/polarity perturbations coexist with HClO.
• Generated NIR-II emission (>1000 nm) with ultralow background.
• Successfully visualized lipid metabolism disorders and oxidative stress simultaneously.

Conclusions:

• NKH-CHOL is the first NIR-II molecular tool for simultaneous visualization of lipid metabolism disorders and oxidative stress in atherosclerosis.
• This probe addresses the critical challenge of early AS detection by improving imaging sensitivity.
• NKH-CHOL holds significant potential for advancing cardiovascular research and clinical diagnostics.