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Synthesis of Monocyte-targeting Peptide Amphiphile Micelles for Imaging of Atherosclerosis
Published on: November 17, 2017
Labeling monocytes with gold nanoparticles to track their recruitment in atherosclerosis with computed tomography
Peter Chhour1, Pratap C Naha2, Sean M O'Neill3
1Department of Radiology, University of Pennsylvania, 3400 Spruce St, 1 Silverstein, Philadelphia, PA 19104, USA; Department of Bioengineering, University of Pennsylvania, 3400 Spruce St, 1 Silverstein, Philadelphia, PA 19104, USA.
Insights
Researchers tracked monocyte accumulation in atherosclerosis using gold nanoparticles and CT imaging. This method successfully visualized gold-labeled monocytes within plaques in mice, offering a new tool for non-invasive imaging.
Area of Science:
- Biomedical Imaging
- Nanotechnology
- Cardiovascular Research
Background:
- Monocyte recruitment into atherosclerotic plaques leads to foam cell formation and plaque rupture, a major cause of myocardial infarction.
- Non-invasive imaging of coronary arteries using X-ray computed tomography (CT) is crucial for early detection and management.
- Tracking monocyte accumulation within plaques is essential for understanding disease progression.
Purpose of the Study:
- To develop and evaluate gold nanoparticles as contrast agents for CT imaging of monocyte accumulation in atherosclerosis.
- To assess the safety and efficacy of gold nanoparticle-labeled monocytes in an animal model.
- To demonstrate the feasibility of non-invasive CT imaging of monocyte trafficking in atherosclerotic plaques.
Main Methods:
- Synthesis and characterization of gold nanoparticles stabilized with various ligands.
- In vitro evaluation of nanoparticle formulations with monocyte cell lines for cytotoxicity, cytokine release, and cell uptake.
- In vivo studies involving injection of gold-labeled primary monocytes into apolipoprotein E deficient mice and subsequent microCT imaging.
- Biodistribution analysis and electron microscopy of plaque tissues.
Main Results:
- 11-MUDA capped gold nanoparticles showed minimal cytotoxicity and high uptake by monocytes without affecting viability or cytokine release.
- MicroCT imaging revealed a significant increase in aortic attenuation in mice receiving gold-labeled monocytes compared to controls.
- Electron microscopy confirmed the presence of gold nanoparticles within monocytes inside atherosclerotic plaques.
Conclusions:
- Gold nanoparticles are effective cell-labeling contrast agents for CT imaging.
- This approach enables non-invasive tracking of monocyte accumulation in atherosclerotic plaques.
- The study demonstrates the potential of this technique for diagnosing and monitoring cardiovascular disease.
Abstract:
Monocytes are actively recruited from the circulation into developing atherosclerotic plaques. In the plaque, monocytes differentiate into macrophages and eventually form foam cells. Continued accumulation of foam cells can lead to plaque rupture and subsequent myocardial infarction. X-ray computed tomography (CT) is the best modality to image the coronary arteries non-invasively, therefore we have sought to track the accumulation of monocytes into atherosclerotic plaques using CT. Gold nanoparticles were synthesized and stabilized with a variety of ligands. Select formulations were incubated with an immortalized monocyte cell line in vitro and evaluated for cytotoxicity, effects on cytokine release, and cell uptake. These data identified a lead formulation, 11-MUDA capped gold nanoparticles, to test for labeling primary monocytes. The formulation did not the affect the viability or cytokine release of primary monocytes and was highly taken up by these cells. Gold labeled primary monocytes were injected into apolipoprotein E deficient mice kept on Western diet for 10 weeks. Imaging was done with a microCT scanner. A significant increase in attenuation was measured in the aorta of mice receiving the gold labeled cells as compared to control animals. Following the experiment, the biodistribution of gold was evaluated in major organs. Additionally, plaques were sectioned and examined with electron microscopy. The results showed that gold nanoparticles were present inside monocytes located within plaques. This study demonstrates the feasibility of using gold nanoparticles as effective cell labeling contrast agents for non-invasive imaging of monocyte accumulation within plaques with CT.
