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Synthesis of Monocyte-targeting Peptide Amphiphile Micelles for Imaging of Atherosclerosis
Published on: November 17, 2017
Molecular imaging of macrophages in atherosclerotic plaques using bimodal PEG-micelles
Willem J M Mulder1, Gustav J Strijkers, Karen C Briley-Saboe
1Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Abstract:
Pegylated, fluorescent, and paramagnetic micelles were developed. The micelles were conjugated with macrophage scavenger receptor (MSR)-specific antibodies. The abdominal aortas of atherosclerotic apoE-KO mice were imaged with T(1)-weighted high-resolution MRI before and 24 h after intravenous administration of the contrast agent (CA). Pronounced signal enhancement (SE) (up to 200%) was observed for apolipoprotein E knockout (apoE-KO) mice that were injected with MSR-targeted micelles, while the aortic vessel wall of mice injected with nontargeted micelles showed little SE. To allow fluorescence microscopy and optical imaging of the excised aorta, the micelles were made fluorescent by incorporating either a quantum dot (QD) in the micelle corona or rhodamine lipids in the micelle. Ultraviolet (UV) illumination of the aorta allowed the identification of regions with high macrophage content, while MSR-targeted rhodamine micelles could be detected with fluorescence microscopy and were found to be associated with macrophages. In conclusion, this study demonstrates that macrophages in apoE-KO mice can be effectively and specifically detected by molecular MRI and optical methods upon administration of a pegylated micellar CA.
Insights
Researchers developed targeted micelles for imaging macrophages in atherosclerosis. These micelles showed significant signal enhancement in MRI scans of atherosclerotic mice, enabling specific detection of macrophages using molecular MRI and optical methods.
Area of Science:
- Biomedical Imaging
- Nanotechnology
- Cardiovascular Research
Background:
- Atherosclerosis is characterized by macrophage accumulation in arterial walls.
- Early and specific detection of macrophages is crucial for assessing atherosclerotic plaque burden.
- Current imaging techniques may lack the specificity for targeted macrophage visualization.
Purpose of the Study:
- To develop and evaluate novel pegylated, fluorescent, and paramagnetic micelles for targeted imaging of macrophages.
- To assess the efficacy of MSR-specific antibody-conjugated micelles in detecting macrophages in atherosclerotic mice using MRI and optical methods.
- To investigate the potential of these micelles as a contrast agent for molecular MRI and fluorescence imaging.
Main Methods:
- Development of multifunctional micelles (pegylated, fluorescent, paramagnetic) conjugated with MSR-specific antibodies.
- Intravenous administration of targeted and non-targeted micelles in atherosclerotic apoE-KO mice.
- High-resolution T1-weighted MRI imaging of abdominal aortas before and after contrast agent administration.
- Fluorescence microscopy and UV illumination for optical imaging of excised aortas.
Main Results:
- MSR-targeted micelles demonstrated pronounced signal enhancement (up to 200%) in the aortic walls of apoE-KO mice via MRI.
- Non-targeted micelles showed minimal signal enhancement, confirming the specificity of the targeted approach.
- Fluorescently labeled targeted micelles were successfully detected in association with macrophages in excised aortas.
- Molecular MRI and optical methods effectively detected macrophages in atherosclerotic mice.
Conclusions:
- Pegylated, MSR-targeted micelles serve as effective contrast agents for molecular MRI.
- These targeted micelles specifically detect and visualize macrophages in atherosclerotic plaques.
- The developed imaging approach offers a promising tool for early diagnosis and monitoring of atherosclerosis.
