The broad subject of this Biomedical Research Partnership (BRP) application is the development of novel multidimensional nanotechnologies for sensitive and specific imaging of molecular epitopes that are etiologic for atherosclerosis. The unifying hypothesis is that targeted molecular imaging with novel paramagnetic perfluorocarbon emulsion nanoparticle contrast agents can delineate selected molecular features of atherosclerotic lesions that are critical determinants of early lesion growth and later lesion instability. Noninvasive and early detection of these situations could enhance patient management and potentially reduce the incidence of myocardial infarction and stroke. The long-range goal is to produce a targeted nanoparticle contrast agent characterized by: 1) flexible targeting options depending on the binding ligand selected, 2) flexible imaging choices based on contrast mechanism best suited to the pathology in question, and 3) flexible opportunities for local delivery of therapeutic agents coupled directly with image-based quantification of local nanoparticle deposition. The technology is expected to enable early noninvasive detection of a variety of pathologies, convenient serial outpatient evaluation, and site-targeted delivery of therapeutics as clinically indicated. Stable and safe self-assembling nanoparticles will be developed, refined, and tested for visualization of pathological epitopes with the use of magnetic resonance imaging (MRI). Corporate partners who are involved in the research and intended commercialization are Kereos, Inc., Philips Medical Systems, Bristol-Myers Squibb Medical Imaging, and Dow Chemical.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL073646-02
Application #
6917866
Study Section
Special Emphasis Panel (ZRG1-SRB-J (50))
Program Officer
Buxton, Denis B
Project Start
2004-07-15
Project End
2009-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
2
Fiscal Year
2005
Total Cost
$1,495,310
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Vemuri, Chandu; Upadhya, Gundumi A; Arif, Batool et al. (2018) Antithrombin Perfluorocarbon Nanoparticles Improve Renal Allograft Function in a Murine Deceased Criteria Donor Model. Transplant Direct 4:e384
Moore, Jeremy K; Chen, Junjie; Pan, Hua et al. (2018) Quantification of vascular damage in acute kidney injury with fluorine magnetic resonance imaging and spectroscopy. Magn Reson Med 79:3144-3153
Kabir, Ashraf Ul; Lee, Tae-Jin; Pan, Hua et al. (2018) Requisite endothelial reactivation and effective siRNA nanoparticle targeting of Etv2/Er71 in tumor angiogenesis. JCI Insight 3:
Yan, Huimin; Zhou, Hui-Fang; Akk, Antonina et al. (2016) Neutrophil Proteases Promote Experimental Abdominal Aortic Aneurysm via Extracellular Trap Release and Plasmacytoid Dendritic Cell Activation. Arterioscler Thromb Vasc Biol 36:1660-1669
Yan, Huimin; Duan, Xin; Pan, Hua et al. (2016) Suppression of NF-?B activity via nanoparticle-based siRNA delivery alters early cartilage responses to injury. Proc Natl Acad Sci U S A 113:E6199-E6208
Palekar, Rohun U; Jallouk, Andrew P; Myerson, Jacob W et al. (2016) Inhibition of Thrombin With PPACK-Nanoparticles Restores Disrupted Endothelial Barriers and Attenuates Thrombotic Risk in Experimental Atherosclerosis. Arterioscler Thromb Vasc Biol 36:446-55
Palekar, Rohun U; Vemuri, Chandu; Marsh, Jon N et al. (2016) Antithrombin nanoparticles inhibit stent thrombosis in ex vivo static and flow models. J Vasc Surg 64:1459-1467
Esser, Alison K; Schmieder, Anne H; Ross, Michael H et al. (2016) Dual-therapy with ?v?3-targeted Sn2 lipase-labile fumagillin-prodrug nanoparticles and zoledronic acid in the Vx2 rabbit tumor model. Nanomedicine 12:201-11
Jallouk, Andrew P; Palekar, Rohun U; Pan, Hua et al. (2015) Modifications of natural peptides for nanoparticle and drug design. Adv Protein Chem Struct Biol 98:57-91
Hughes, Michael S; McCarthy, John E; Bruillard, Paul J et al. (2015) Entropy vs. Energy Waveform Processing: A Comparison Based on the Heat Equation. Entropy (Basel) 17:3518-3551

Showing the most recent 10 out of 85 publications