Prevention of Allergic Disease Using Nanomaterials

描述（由申请人提供）：纳米技术，在分子水平上使用纳米材料，是一个多学科的科学领域，正在经历指数增长，并在科学的所有部门中有广泛的应用。纳米材料的一种形式，富勒烯，是足球形状的碳笼，可以用各种分子官能化和衍生化。鉴于其独特的结构和性质，富勒烯正在被研究作为一种新的和/或改进的方式来诊断，监测和治疗某些疾病。然而，没有研究检查这些化合物对过敏反应的影响。肥大细胞（MC）和外周血嗜碱性粒细胞（PBB）是重要的效应细胞，传统上与过敏反应的启动和传播有关。最近的研究表明，这些细胞也可能是炎症和先天免疫的重要调节因子。我们发现了一种意想不到的新机制，通过这种机制，使用富勒烯抑制过敏过程。我们假设富勒烯纳米材料可能是一种迄今为止尚未认识到的，并且可能有用的抑制受MC和PBB反应严重影响的疾病的方法。此外，我们假设这些分子可以以允许它们特异性靶向MC和PBB的方式被操纵。为了检验这些假设，我们将使用原代人MC和PBB的组合，以及人类疾病的鼠模型，包括过敏症、关节炎和多发性硬化症。我们的目标是确定富勒烯是否可以抑制那些先前已被证明具有较大MC/PBB影响的疾病的诱导和进展。这一全新的研究项目可能为新的策略奠定基础，不仅用于过敏治疗，而且用于那些由MC和PBB反应介导的疾病，如关节炎和自身免疫性疾病。 肥大细胞是重要的效应细胞，传统上与引发和传播过敏反应有关，但最近的研究表明，这些细胞也可能是关节炎，多发性硬化症和其他自身免疫性疾病的重要调节因子。我们发现了一种新的机制，通过这种机制，过敏过程被称为富勒烯的纳米材料所抑制。该提案的目标是确定这些分子是否可能成为MC介导疾病的可行新疗法。PHS 398/2590（2004年9月修订，2006年4月重新印发）

DESCRIPTION (provided by applicant): Nanotechnology, the use of nanomaterials at the molecular level, is a multidisciplinary scientific field undergoing exponential growth and has broad applications among all divisions of science. One form of nanomaterials, fullerenes, is soccer-ball-shaped carbon cages that can be functionalized and derivatized with a wide array of molecules. Given their unique structure and properties, fullerenes are being investigated as a new and/or improved way to diagnose, monitor, and treat certain conditions. However, no studies have examined the effects these compounds have on the allergic response. Mast cells (MC) and peripheral blood basophils (PBB) are important effector cells that have traditionally been associated with initiating and propagating the allergic response. Recent studies suggest that these cells may also be important regulators of inflammation and innate immunity. We have discovered an unexpected and new mechanism through which the allergic process is inhibited using fullerenes. We hypothesize that fullerene nanomaterials may be a heretofore unrecognized, and potentially useful, way to inhibit diseases that are critically affected by MC and PBB responses. Further, we hypothesize these molecules may be manipulated in such a way that allows them to specifically target MC and PBB. To test these hypotheses we will use a combination of primary human MC and PBB in addition to murine models of human disease including allergy, arthritis, and multiple sclerosis. Our goal is to determine if fullerenes can inhibit the induction and progression of those diseases that have previously been shown to have a large MC/PBB influence. This completely novel research program may lay the foundation for new strategies not only for allergy treatment but for those diseases that are mediated by MC and PBB responses such as arthritis and autoimmune disease. PUBLIC HEALTH RELEVANCE Mast cells are important effector cells that have traditionally been associated with initiating and propagating the allergic response but recent studies suggest that these cells may also be important regulators of arthritis, multiple sclerosis, and other autoimmune disorders. We have discovered a new mechanism through which the allergic process is inhibited using nanomaterials called fullerenes. The goal of this proposal is to determine if these molecules could potentially be a viable new therapy for MC-mediated disease. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page