Endothelial α ν β 3 Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis
| Autor: | J. David Robertson, Patrick M. Winter, John S. Allen, Samuel A. Wickline, Elizabeth K. Lacy, Grace Hu, Shelton D. Caruthers, Todd A. Williams, Thomas D. Harris, Gregory M. Lanza, Anne M. Neubauer, Huiying Zhang, Anne H. Schmieder |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Pathology
medicine.medical_specialty Endothelium Angiogenesis Integrin Angiogenesis Inhibitors Hyperlipidemias Biology Neovascularization Drug Delivery Systems Cyclohexanes medicine.artery medicine Animals Aorta Abdominal Fumagillin Aorta Neovascularization Pathologic Vascular disease Atherosclerosis Integrin alphaVbeta3 medicine.disease Magnetic Resonance Imaging Nanostructures medicine.anatomical_structure Vasa vasorum Fatty Acids Unsaturated biology.protein Endothelium Vascular Rabbits medicine.symptom Cardiology and Cardiovascular Medicine Sesquiterpenes medicine.drug |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 26:2103-2109 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.0000235724.11299.76 |
| Popis: | Objective— Angiogenic expansion of the vasa vasorum is a well-known feature of progressive atherosclerosis, suggesting that antiangiogenic therapies may stabilize or regress plaques. α ν β 3 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 α ν β 3 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 α ν β 3 -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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|