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Human ferritin cages for imaging vascular macrophages
Masahiro Terashima1, Masaki Uchida, Hisanori Kosuge
1Division of Cardiovascular Medicine, Stanford University, Stanford, CA 94305-5233, USA.
Abstract:
Atherosclerosis is a leading cause of death worldwide. Macrophages are key components of vascular inflammation, which contributes to the development and complications of atherosclerosis. Ferritin, an iron storage and transport protein, has been found to accumulate in macrophages in human atherosclerotic plaques. We hypothesized that ferritin could serve as an intrinsic nano-platform to target delivery of imaging agents to vascular macrophages to detect high-risk atherosclerotic plaques. Here we show that engineered human ferritin protein cages, either conjugated to the fluorescent Cy5.5 molecule or encapsulating a magnetite nanoparticle, are taken up in vivo by macrophages in murine atherosclerotic carotid arteries and can be imaged by fluorescence and magnetic resonance imaging. These results indicate that human ferritin can serve as a nanoparticle platform to image vascular inflammation in vivo.
Insights
Engineered ferritin protein cages target macrophages in atherosclerotic plaques. This novel nanoparticle platform enables in vivo imaging of vascular inflammation, aiding detection of high-risk plaques.
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.
