Endothelial ανβ3 integrin-targeted fumagillin nanoparticles inhibit angiogenesis in atherosclerosis

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Abstract

OBJECTIVE - Angiogenic expansion of the vasa vasorum is a well-known feature of progressive atherosclerosis, suggesting that antiangiogenic therapies may stabilize or regress plaques. ανβ3 Integrin-targeted paramagnetic nanoparticles were prepared for noninvasive assessment of angiogenesis in early atherosclerosis, for site-specific delivery of antiangiogenic drug, and for quantitative follow-up of response. METHODS AND RESULTS - Expression of ανβ3 integrin by vasa vasorum was imaged at 1.5 T in cholesterol-fed rabbit aortas using integrin-targeted paramagnetic nanoparticles that incorporated fumagillin at 0 μg/kg or 30 μg/kg. Both formulations produced similar MRI signal enhancement (16.7%±1.1%) when integrated across all aortic slices from the renal arteries to the diaphragm. Seven days after this single treatment, integrin-targeted paramagnetic nanoparticles were readministered and showed decreased MRI enhancement among fumagillin-treated rabbits (2.9%±1.6%) but not in untreated rabbits (18.1%±2.1%). In a third group of rabbits, nontargeted fumagillin nanoparticles did not alter vascular ανβ3-integrin expression (12.4%±0.9%; P>0.05) versus the no-drug control. In a second study focused on microscopic changes, fewer microvessels in the fumagillin-treated rabbit aorta were counted compared with control rabbits. CONCLUSIONS - This study illustrates the potential of combined molecular imaging and drug delivery with targeted nanoparticles to noninvasively define atherosclerotic burden, to deliver effective targeted drug at a fraction of previous levels, and to quantify local response to treatment. © 2006 American Heart Association, Inc.

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APA

Winter, P. M., Neubauer, A. M., Caruthers, S. D., Harris, T. D., Robertson, J. D., Williams, T. A., … Lanza, G. M. (2006). Endothelial ανβ3 integrin-targeted fumagillin nanoparticles inhibit angiogenesis in atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 26(9), 2103–2109. https://doi.org/10.1161/01.ATV.0000235724.11299.76

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