Human ferritin cages for imaging vascular macrophages

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cardiovascular Research

Background:

• Atherosclerosis is a major global cause of mortality.
• Macrophages play a critical role in vascular inflammation and atherosclerosis progression.
• Ferritin, an iron-binding protein, accumulates in macrophages within atherosclerotic lesions.

Purpose of the Study:

• To investigate the potential of engineered human ferritin as a nanoparticle platform for targeted delivery of imaging agents.
• To assess ferritin's capability to target vascular macrophages in vivo.
• To evaluate the utility of ferritin-based nanoparticles for imaging high-risk atherosclerotic plaques.

Main Methods:

• Engineered human ferritin protein cages were created, conjugated with a fluorescent dye (Cy5.5) or loaded with magnetite nanoparticles.
• These ferritin nanoparticles were administered in vivo to mice with atherosclerotic carotid arteries.
• Imaging was performed using fluorescence and magnetic resonance imaging (MRI) techniques to detect nanoparticle uptake in macrophages.

Main Results:

• Engineered ferritin nanoparticles were successfully taken up by macrophages within atherosclerotic carotid arteries in vivo.
• Fluorescence imaging demonstrated the localization of Cy5.5-conjugated ferritin to plaque macrophages.
• MRI confirmed the presence and distribution of magnetite-encapsulated ferritin within the atherosclerotic lesions.
• These findings validate ferritin's ability to serve as a targeted imaging agent for vascular inflammation.

Conclusions:

• Human ferritin can be engineered into a versatile nanoparticle platform for biomedical applications.
• Ferritin-based nanoparticles effectively target and enable in vivo imaging of macrophages in atherosclerosis.
• This approach holds promise for non-invasive detection and characterization of high-risk atherosclerotic plaques.