RGD-conjugated human ferritin nanoparticles for imaging vascular inflammation and angiogenesis in experimental carotid and aortic disease

Purpose: 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. Procedures: 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 nearinfrared fluorescence imaging. Results: 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. Conclusions: 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.