- Meeting abstract
- Open Access
2089 Detecting inflammation in atherosclerosis using protein cage nanoparticles as cellular imaging agents
© Terashima et al; licensee BioMed Central Ltd. 2008
- Published: 22 October 2008
- Confocal Fluorescence Microscopy
- Protein Cage
- Heavy Chain Ferritin
- Ligate Carotid Artery
- Carotid Ligation
Macrophages are important imaging targets for identifying and monitoring high-risk atherosclerotic plaque. Human heavy chain ferritin (HFn) is a promising nanoscale protein cage platform for cellular and molecular imaging, demonstrating substantial in vitro uptake by macrophages.
To evaluate the in vivo uptake and distribution of MRI and fluorescent HFn nanoparticles in mouse atherosclerosis.
A macrophage-rich carotid lesion in FVB mice (n = 12) was induced as follows: high fat diet for 4 weeks then diabetes induction by 5 daily intraperitoneal injections of streptozotocin. Two weeks later, we performed carotid ligation of the left common carotid artery. In the first group of mice (n = 5), an MRI form of HFn containing iron oxide (HFn-3000Fe) was injected via tail vein (25 mgFe/kg) 2 weeks after carotid ligation. Mice were sacrificed 48 hours after injection and HFn-Fe uptake was assessed histologically by Perl's iron staining. In the second group of mice (4 diseased and 3 sham), HFn was labeled with the near-infrared (NIR) fluorophore Cy5.5 (HFn-Cy5.5: 4.6 Cy5.5 dye/cage) and injected via tail vein (8 nmol of Cy5.5) 2 weeks after carotid ligation. Mice were imaged serially by in vivo NIR imaging up to 48 hours. At 48 hours, both carotid arteries were exposed for in situ NIR imaging, and then removed for ex vivo NIR imaging. All mice were imaged under 2% isoflurane anesthesia using the MaestroTM in-vivo imaging system (CRI, Woburn, MA). After the NIR imaging, both carotid arteries were removed and cut into 2 mm sections for confocal fluorescence microscopy to detect HFn-Cy5.5 colocalized with macrophages.
Human ferritin protein cages labeled with iron oxide or fluorophore localize to macrophages in the atherosclerotic lesions in vivo. These initial results encourage further investigation into the use of protein cage architectures as a novel platform for MR or NIR contrast agents for detecting macrophage infiltration within atherosclerotic plaques.
This article is published under license to BioMed Central Ltd.