RGD-Conjugated Human Ferritin Nanoparticles for Imaging Vascular Inflammation and Angiogenesis in Experimental Carotid and Aortic Disease
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Inflammation and angiogenesis are important contributors to vascular disease. We evaluated imaging both of these biological processes, using Arg–Gly–Asp (RGD)-conjugated human ferritin nanoparticles (HFn), in experimental carotid and abdominal aortic aneurysm (AAA) disease.
Macrophage-rich carotid lesions were induced by ligation in hyperlipidemic and diabetic FVB mice (n = 16). AAAs were induced by angiotensin II infusion in apoE−/− mice (n=10). HFn, with or without RGD peptide, was labeled with Cy5.5 and injected intravenously for near-infrared fluorescence imaging.
RGD-HFn showed significantly higher signal than HFn in diseased carotids and AAAs relative to non-diseased regions, both in situ (carotid: 1.88 ± 0.30 vs. 1.17 ± 0.10, p = 0.04; AAA: 2.59 ± 0.24 vs. 1.82 ± 0.16, p = 0.03) and ex vivo. Histology showed RGD-HFn colocalized with macrophages in carotids and both macrophages and neoangiogenesis in AAA lesions.
RGD-HFn enhances vascular molecular imaging by targeting both vascular inflammation and angiogenesis, and allows more comprehensive detection of high-risk atherosclerotic and aneurysmal vascular diseases.
Key wordsVascular disease Nanoparticles Inflammation Angiogenesis Atherosclerosis Aneurysms RGD Ferritin
We thank Dr. Matthew Bogyo and his laboratory for their assistance with mouse fluorescence molecular tomography. We thank support from the National Institutes of Health (R21 EB005364, R01 HL078678, P50 HL083800).
Dr. McConnell's laboratory receives research support from GE Healthcare and he is on a scientific advisory board for Kowa, Inc. Dr. Dalman's laboratory receives AAA research support from Medtronic AVE and Carolus Pharmaceuticals. The other authors have no potential conflicts of interest.
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