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Endothelial α ν β 3 Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis
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. 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.
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“A team led by Wickline and Lanza107 has shown that a single injection of αVβ3 integrin-targeted paramagnetic nanoparticles for site-specific delivery of the anti-angiogenic drug fumagillin is enough to inhibit angiogenesis in a rabbit model.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [107]
In the citing paper
“In a follow-up study the same group demonstrated that these nanoparticles decreased the burden of aortic angiogenesis for 3 weeks after treatment”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [107]
In the citing paper
“and that this effect was prolonged when applied in combination with oral atorvastatin (Lipitor; Pfizer) administration.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [107]
In the citing paper
“This was determined using αVβ3 integrin-specific MRI, thus representing a potential strategy for an anti-angiogenic therapeutic regimen107,108 (FIG. 3c).”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [107]
In the citing paper
“This was the first study to show the therapeutic potential of combined molecular imaging and drug delivery with targeted nanoparticles in a rabbit model of atherosclerosis.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [107]
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Self-citation
Metadata
- Authors
- Winter, P. M., Neubauer, A. M., Caruthers, S. D., Harris, T. D., Robertson, J. D., Williams, T. A., Schmieder, A. H., Hu, G., Allen, J. S., Lacy, E. K., Zhang, H., Wickline, S. A., & Lanza, G. M.
- Affiliations
- Washington University in St. Louis (US)
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2006-09
- Volume
- 26
- Issue
- 9
- Pages
- 2103-2109
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2112285684
- Cited by
- 379
- References
- 31
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 15 · 2021: 16 · 2020: 13 · 2019: 17 · 2018: 14 · 2017: 23 · 2016: 12 · 2015: 22 · 2014: 29 · 2013: 17 · 2012: 37
- FWCI
- 13.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL073646, HL-73646, R01HL078631, HL 78631)
- National Cancer Institute (N01 CO 37007)
- National Institute of Biomedical Imaging and Bioengineering (R01EB001704, EB-01704)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Keywords
- alpha v beta 3 integrin, fumagillin, targeted nanoparticles, angiogenesis inhibition, atherosclerosis, vasa vasorum, paramagnetic nanoparticles, magnetic resonance imaging, molecular imaging, targeted drug delivery, atherosclerotic plaque, rabbit aorta
- MeSH terms
- Animals, Aorta, Abdominal, Cyclohexanes, Endothelium, Vascular, Fatty Acids, Unsaturated, Hyperlipidemias, Magnetic Resonance Imaging, Neovascularization, Pathologic, Rabbits, Sesquiterpenes, Drug Delivery Systems, Angiogenesis Inhibitors, Integrin alphaVbeta3, Nanostructures, Atherosclerosis
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