Using Nanomaterials to Inhibit Mast Cell/Basophil-Associated Disease

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，正在呈指数级增长，在所有科学部门中都有广泛的应用。富勒烯是纳米材料的一种形式，它是足球形状的碳笼，可以用多种分子进行功能化和衍生化。由于其独特的结构和性质，富勒烯被研究作为一种新的和/或改进的方法来诊断、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的机制，通过这种机制富勒烯可以抑制过敏过程。我们假设富勒烯纳米材料可能是一种迄今为止未被认识到的、潜在有用的方法，可以抑制受MC和PBB反应严重影响的疾病。此外，我们假设这些分子可能以这样一种方式被操纵，使它们能够特异性靶向MC和PBB。为了验证这些假设，我们将使用原发人类MC和PBB的组合，以及人类疾病（包括过敏、关节炎和多发性硬化症）的小鼠模型。我们的目标是确定富勒烯是否可以抑制那些先前被证明具有较大MC/PBB影响的疾病的诱导和进展。这一全新的研究项目可能不仅为过敏治疗，而且为那些由MC和PBB反应介导的疾病（如关节炎和自身免疫性疾病）的新策略奠定基础。

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. Project Narrative: Allergic diseases, arthritis, multiple sclerosis, and other autoimmune diseases are huge public health problems that affect millions of Americans. These diseases are induced and propagated largely by mast cells and basophils. We have discovered that certain nanomaterials block their noxious effects and thus may be a new way to control those diseases that are largely mediated by these cells types.