Asthma is a chronic inflammatory lung disease that affects an estimated 23 million Americans (16 million adults), 12 million of whom experience at least one asthma attack annually. The symptoms of asthma cause significant economic burden on the healthcare systems ($18B in 2008) as well as dramatic impact on the quality of patients'lives. Asthma is characterized by airway inflammation and edema. Recently, the long recognized increase in airway wall microvessel density and expanded blood volume have been suggested to contribute significantly to lung function. This project combines the recognized expertise of Professor Elizabeth Wagner, PhD (PI) in pulmonary angiogenesis physiology and Professor Gregory M. Lanza, MD PhD (PD/PI), whose nanomedicine-based molecular imaging and therapy is well known, particularly in the context of angiogenesis in cancer and atherosclerosis. The overarching hypotheses of this proposal are to use nanomedicine approach to noninvasively characterize bronchial angiogenesis (new vessel formation), to deliver acute antiangiogenic therapy to reduce airway remodeling and improve pulmonary function, and to maintain the acute benefits of this new treatment with standard-of-care low dose steroids.

Public Health Relevance

Asthma is pathologically characterized by airway structure remodeling resulting from damage to airway epithelium, eosinophil infiltration, smooth muscle hyperplasia, and basement membrane thickening. Increases in the number and size of vessels within the airway wall have long been recognized as an element of asthma remodeling, occurring in mild, moderate, and severe asthmatic lungs of patients young and old. However, recent studies now point to a functional relationship between the severity of chronic asthma and increasing microvessel density, suggesting that microvascular blood volume contributes significantly to airway obstruction. The overarching hypotheses of this proposal are that nanomedicine approach can be used effectively: 1) to noninvasively quantify bronchial angiogenesis, 2) to deliver acute antiangiogenic therapy to reduce airway remodeling and improve pulmonary function, and 3) to maintain the acute benefits of antiangiogenic treatment with low dose steroids. This nanomedicine approach to asthma employs quantitative image stratification and targeted prodrug nanotherapy in conjunction with current standard of care drugs to offer a clinically translatable approach to ameliorate the progression of moderate to severe asthma ultimately to reduce hospitalizations and home health-care costs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL113392-01
Application #
8274016
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Noel, Patricia
Project Start
2012-04-09
Project End
2017-02-28
Budget Start
2012-04-09
Budget End
2013-02-28
Support Year
1
Fiscal Year
2012
Total Cost
$662,009
Indirect Cost
$144,108
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Cui, Grace; Akers, Walter J; Scott, Michael J et al. (2018) Diagnosis of LVAD Thrombus using a High-Avidity Fibrin-Specific 99mTc Probe. Theranostics 8:1168-1179
Wu, Lina; Wen, Xiaofei; Wang, Xiance et al. (2018) Local Intratracheal Delivery of Perfluorocarbon Nanoparticles to Lung Cancer Demonstrated with Magnetic Resonance Multimodal Imaging. Theranostics 8:563-574
Kotagiri, Nalinikanth; Cooper, Matthew L; Rettig, Michael et al. (2018) Radionuclides transform chemotherapeutics into phototherapeutics for precise treatment of disseminated cancer. Nat Commun 9:275
Ross, Michael H; Esser, Alison K; Fox, Gregory C et al. (2017) Bone-Induced Expression of Integrin ?3 Enables Targeted Nanotherapy of Breast Cancer Metastases. Cancer Res 77:6299-6312
Lanza, Gregory M; Cui, Grace; Schmieder, Anne H et al. (2017) An unmet clinical need: The history of thrombus imaging. J Nucl Cardiol :
Moldobaeva, Aigul; Jenkins, John; Zhong, Qiong et al. (2017) Lymphangiogenesis in rat asthma model. Angiogenesis 20:73-84
Lanza, Gregory M; Jenkins, John; Schmieder, Anne H et al. (2017) Anti-angiogenic Nanotherapy Inhibits Airway Remodeling and Hyper-responsiveness of Dust Mite Triggered Asthma in the Brown Norway Rat. Theranostics 7:377-389
Pan, Dipanjan; Pham, Christine T N; Weilbaecher, Katherine N et al. (2016) Contact-facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery. Wiley Interdiscip Rev Nanomed Nanobiotechnol 8:85-106
Zhong, Qiong; Jenkins, John; Moldobaeva, Aigul et al. (2016) Effector T Cells and Ischemia-Induced Systemic Angiogenesis in the Lung. Am J Respir Cell Mol Biol 54:394-401
Eldridge, Lindsey; Moldobaeva, Aigul; Zhong, Qiong et al. (2016) Bronchial Artery Angiogenesis Drives Lung Tumor Growth. Cancer Res 76:5962-5969

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