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Updated: Jun 6, 2026
Synthesis of Monocyte-targeting Peptide Amphiphile Micelles for Imaging of Atherosclerosis
Published on: November 17, 2017
Detection of macrophages via paramagnetic vesicles incorporating oxidatively tailored cholesterol ester: an approach
Andrei Maiseyeu1, Georgeta Mihai, Sashwati Roy
1Davis Heart & Lung Research Institute, Room 110, 473 W 12th Avenue, Columbus, OH 43210-1252, USA.
Aim:
Macrophages play a key role in the initiation, progression and complications of atherosclerosis. In this article we describe the synthesis of biocompatible, paramagnetic, fluorescent phosphatidylserine vesicles containing cholesterol ester with a free carboxylic acid function and its use for targeted imaging of macrophages.
Methods & Results:
We synthesized anionic vesicles containing a combination of phosphatidylserine and a novel synthetic oxidized cholesterol ester derivative (cholesterol-9-carboxynonanoate [9-CCN]). In vitro studies to characterize particle size, MRI relaxation times and stability were performed. Vesicles containing 9-CCN demonstrated enhanced ability to bind human low-density lipoprotein and to be internalized by macrophages. Experiments in cultured macrophages with 9-CCN vesicles, alone and in the presence of low-density lipoprotein, indicated uptake of vesicles through scavenger receptor and integrin-dependent pathways. In vivo MRI using 9-CCN vesicles containing gadolinium in a rabbit model of atherosclerosis revealed protracted enhancement of 9-CCN vesicles and colocalization with arterial macrophages not seen with control vesicles. Pharmacokinetic experiments demonstrated prolonged plasma residence time of 9-CCN vesicles, perhaps due to its capacity to bind to low-density lipoprotein.
Conclusion:
Vesicles containing 9-CCN demonstrate prolonged plasma and plaque retention in experimental atherosclerosis. Such a strategy may represent a simple yet clinically relevant approach for macrophage imaging.
Insights
New phosphatidylserine vesicles target macrophages in atherosclerosis. These biocompatible, paramagnetic, fluorescent vesicles show prolonged retention in plaques, enabling enhanced macrophage imaging for potential clinical use.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cardiovascular Research
Background:
- Macrophages are central to atherosclerosis development and complications.
- Targeted imaging of macrophages is crucial for understanding and treating atherosclerosis.
- Current imaging methods face limitations in specificity and retention.
Purpose of the Study:
- To synthesize and characterize novel biocompatible, paramagnetic, fluorescent phosphatidylserine vesicles.
- To evaluate the targeted uptake and retention of these vesicles by macrophages in vitro and in vivo.
- To assess the potential of these vesicles for macrophage imaging in experimental atherosclerosis.
Main Methods:
- Synthesis of anionic phosphatidylserine vesicles incorporating cholesterol-9-carboxynonanoate (9-CCN).
- In vitro characterization of vesicle size, MRI relaxation times, stability, and low-density lipoprotein (LDL) binding.
- Macrophage uptake studies using cultured cells and assessment of involved pathways (scavenger receptor, integrin).
- In vivo MRI in a rabbit atherosclerosis model using gadolinium-loaded 9-CCN vesicles.
- Pharmacokinetic analysis of vesicle plasma residence time.
Main Results:
- 9-CCN vesicles exhibited enhanced binding to LDL and efficient internalization by macrophages via scavenger receptor and integrin pathways.
- In vivo MRI demonstrated prolonged enhancement and colocalization with arterial macrophages in atherosclerotic rabbits.
- Vesicles showed prolonged plasma residence time, potentially due to LDL binding.
- Control vesicles did not show similar enhancement or colocalization.
Conclusions:
- Phosphatidylserine vesicles containing 9-CCN demonstrate prolonged retention in atherosclerotic plaques.
- This strategy offers a promising approach for targeted macrophage imaging.
- The developed vesicles represent a clinically relevant tool for atherosclerosis research and potential diagnostics.
