Targeted Iron Oxide Particles for In Vivo Magnetic Resonance Detection of Atherosclerotic Lesions With Antibodies Directed to Oxidation-Specific Epitopes
Open accessAbstract
Objectives The aim of this study was to determine whether iron oxide particles targeted to oxidation-specific epitopes image atherosclerotic lesions.Background Oxidized low-density lipoprotein plays a major role in atherosclerotic plaque progression and destabilization. Prior studies indicate that gadolinium micelles labeled with oxidation-specific antibodies allow for in vivo detection of vulnerable plaques with magnetic resonance imaging (MRI). However, issues related to biotransformation/retention of gadolinium might limit clinical translation. Iron oxides are recognized as safe and effective contrast agents for MRI. Because the efficacy of passively targeted iron particles remains variable, it was hypothesized that iron particles targeted to oxidation-specific epitopes might increase the utility of this platform.Methods Lipid-coated ultra-small superparamagnetic iron particles (LUSPIOs) (<20 nm) and superparamagnetic iron particles (<40 nm) were conjugated with antibodies targeted to either malondialdehyde-lysine or oxidized phospholipid epitopes. All formulations were characterized, and their in vivo efficacy evaluated in apolipoprotein E deficient mice 24 h after bolus administration of a 3.9-mg Fe/kg dose with MRI. In vivo imaging data were correlated with the presence of oxidation-specific epitopes with immunohistochemistry.Results MRI of atherosclerotic lesions, as manifested by signal loss, was observed after administration of targeted LUSPIOs. Immunohistochemistry confirmed the presence of malondialdehyde-epitopes and iron particles. Limited signal attenuation was observed for untargeted LUSPIOs. Additionally, no significant arterial wall uptake was observed for targeted or untargeted lipid-coated superparamagnetic iron oxide particles, due to their limited ability to penetrate the vessel wall.Conclusions This study demonstrates that LUSPIOs targeted to oxidation-specific epitopes image atherosclerotic lesions and suggests a clinically translatable platform for the detection of atherosclerotic plaque.
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Macrophages and oxidized LDL have been targeted using immunomicelles.
“For example, macrophages and oxidized LDL have been targeted using immunomicelles43,134, and apoptosis has been studied using annexin A5-functionalized nanoparticles135.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [43]
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- Authors
- Briley-Saebo, K. C., Cho, Y. S., Shaw, P. X., Ryu, S. K., Mani, V., Dickson, S., Izadmehr, E., Green, S., Fayad, Z. A., & Tsimikas, S.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Seoul National University (KR)
- University of California San Diego (US)
- Eulji University (KR)
- Corresponding author
- Tsimikas, Sotirios
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 57
- Issue
- 3
- Pages
- 337-347
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC3095034
- OpenAlex
- W2088395836
- Cited by
- 128
- References
- 34
- Citations by year
- 2025: 4 · 2024: 6 · 2023: 2 · 2022: 6 · 2021: 9 · 2020: 8 · 2019: 9 · 2018: 10 · 2017: 5 · 2016: 9 · 2015: 11 · 2014: 9 · 2013: 13 · 2012: 16
- FWCI
- 7.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01 HL71021, R01 HL78667)
- National Institute of Biomedical Imaging and Bioengineering (R01 EB009638)
- Fondation Leducq
- National Institutes of Health (R21 HL091399-01A2)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Keywords
- iron oxide nanoparticles, superparamagnetic iron oxide nanoparticles, oxidation-specific epitopes, atherosclerotic plaque imaging, oxidized LDL, vulnerable plaque, ApoE-deficient mice, gadolinium alternatives, lipid-coated nanoparticles
- MeSH terms
- Animals, Antibodies, Epitopes, Contrast Media, Ferric Compounds, Magnetic Resonance Imaging, Mice, Inbred C57BL, Oxidation-Reduction, Particle Size, Drug Delivery Systems, Mice, Knockout, Atherosclerosis, Mice
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