Antiangiogenic Synergism of Integrin-Targeted Fumagillin Nanoparticles and Atorvastatin in Atherosclerosis

• Published in: JACC. Cardiovascular imaging 2008-09, Vol.1 (5), p.624-634
• Main Authors: Winter, Patrick M., PhD, Caruthers, Shelton D., PhD, Zhang, Huiying, MD, Williams, Todd A., RT, MR, Wickline, Samuel A., MD, FACC, Lanza, Gregory M., MD, PhD, FACC
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - metabolism; Angiogenesis Inhibitors - pharmacology; Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Aorta, Thoracic - pathology; Atherosclerosis - drug therapy; Atherosclerosis - metabolism; Atherosclerosis - pathology; Atorvastatin; Carbocyanines - metabolism; Cardiovascular; Cyclohexanes - metabolism; Cyclohexanes - pharmacology; Disease Models, Animal; Drug Carriers; Drug Synergism; Drug Therapy, Combination; Fatty Acids, Unsaturated - metabolism; Fatty Acids, Unsaturated - pharmacology; Heptanoic Acids - pharmacology; Heterocyclic Compounds, 1-Ring - metabolism; Integrin alphaVbeta3 - metabolism; Liver - drug effects; Liver - pathology; Magnetic Resonance Imaging; Nanoparticles; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Neovascularization, Pathologic - prevention & control; Pyrroles - pharmacology; Rabbits; Sesquiterpenes - metabolism; Sesquiterpenes - pharmacology; Time Factors
• ISSN: 1936-878X; 1876-7591; 1876-7591
• DOI: 10.1016/j.jcmg.2008.06.003

Antiangiogenic Synergism of Integrin-Targeted Fumagillin Nanoparticles and Atorvastatin in Atherosclerosis Patrick M. Winter, Shelton D. Caruthers, Huiying Zhang, Todd A. Williams, Samuel A. Wickline, Gregory M. Lanza The authors describe a clinically translatable method for sustained antiangiogenic treatment of atherosclerosis that combines αν β3 -targeted fumagillin nanoparticles and statin therapy. Site-specific delivery of fumagillin was achieved with perfluorocarbon nanoparticles targeted to the αν β3 -integrin, a biomarker of angiogenic vasculature, which reduced the total drug dose by more than 10,000-fold. The antiangiogenic effects were serially measured in the aortic vasa vasorum with cardiac magnetic resonance molecular imaging using αν β3 -targeted paramagnetic nanoparticles. The acute antiangiogenic effectiveness of a single low dose of αν β3 -targeted fumagillin nanoparticles was maintained for 3 weeks, and atorvastatin prolonged the antiangiogenic effects of fumagillin. In the accompanying editorial, Drs. Arbustini and Gambarin highlight the role of neoangiogenesis in plaque vulnerability and potential implications of antiangiogenic therapy.