Theranostic Approach to Asthma Using Anti-Angiogenic Nanomedicine

使用抗血管生成纳米药物治疗哮喘的方法

• 批准号: 8274016
• 负责人: Gregory M Lanza
• 金额: $ 66.2万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-09 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8274016
• 关键词: Acute; Adult; Affect; American; Angiogenesis Inhibitors; Asthma; Atherosclerosis; Basement membrane; Blood Volume; Blood flow; Caring; Chronic; Collaborations; Development; Disease; Doctor of Philosophy; Dose; Economic Burden; Edema; Elements; Fluorocarbons; Glucocorticoids; Health Care Costs; Healthcare Systems; Histopathology; Home Care Services; Hospitalization; Hyperplasia; Image; Infiltration; Inflammatory; Lipase; Lung; Lung diseases; Malignant Neoplasms; Modeling; Molecular; Molecular Biology; Pathologic; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phospholipids; Physiology; Pre-Clinical Model; Prodrugs; Rattus norvegicus; Research; Respiratory physiology; Role; Severities; Smooth Muscle; Staging; Steroids; Stratification; Structure; Symptoms; Therapeutic Agents; airway epithelium; airway inflammation; airway obstruction; airway remodeling; angiogenesis; antiangiogenesis therapy; base; density; design; eosinophil; experience; fumagillin; functional status; hemodynamics; improved; lung development; molecular imaging; nanomedicine; nanoparticle; nanotherapy; novel; professor; pulmonary function; respiratory; response to injury; spatiotemporal; standard of care; theranostics

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：哮喘是一种慢性炎症性肺部疾病，影响约2300万美国人（1600万成年人），其中1200万人每年至少经历一次哮喘攻击。哮喘的症状对医疗保健系统产生了重大的经济负担（2008年为18B美元），并对患者生活的质量产生了巨大影响。哮喘的特征是气道炎症和水肿。最近，已经建议长期公认的气道壁微血管密度和扩大的血容量增加，从而对肺功能产生显着贡献。 该项目结合了Elizabeth Wagner教授，肺血管生成生理学博士学位（PI）的公认专业知识，以及Gregory M. Lanza教授，医学博士学位（PD/PI），其基于纳米医学的分子成像和治疗是众所周知的，尤其是在癌症和癌症中的血管生成。该提案的总体假设是使用纳米医学方法来表征支气管血管生成（新血管形成），以提供急性的抗血管生成疗法来减少气道重塑并改善肺功能，并维持这种具有这种新的治疗方法的急性益处。 公共卫生相关性：哮喘在病理上的特征是气道结构重塑，导致气道上皮损坏，嗜酸性粒细胞浸润，平滑肌增生和基底膜膜增厚。长期以来，气道壁内血管数量和大小的增加已被认为是哮喘重塑的元素，发生在患者和老年患者的轻度，中度和严重的哮喘肺中。然而，最近的研究现在表明慢性哮喘的严重程度与微血管密度的增加之间存在功能关系，这表明微血管血容量对气道阻塞产生了重大贡献。 该提案的总体假设是可以有效地使用纳米医学方法：1）非侵袭性量化支气管血管生成，2）提供急性的抗血管生成疗法，以减少气道重塑并改善肺功能； 3）维持抗雄激素治疗的急性剂量治疗，可用于低剂量的固定剂。这种对哮喘的纳米医学方法采用定量图像分层和针对性的前药纳米疗法以及当前的护理药物标准药物提供了可提供临床上可翻译的方法来改善中度至重度哮喘的进展，最终以降低住院和家庭保健费用。