Prevention of Allergic Disease Using Nanomaterials

描述(申请人提供)：纳米技术，即在分子水平上使用纳米材料，是一个正在指数级增长的多学科科学领域，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，可以用一系列广泛的分子功能化和衍生化。由于其独特的结构和性质，富勒烯正被研究为诊断、监测和治疗某些疾病的一种新的和/或改进的方法。然而，还没有研究检验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，传统上与启动和传播过敏反应有关。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素。我们发现了一种意想不到的新机制，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到目前为止还没有被认识到的，并且可能有用的方法，来抑制受到MC和PBB反应严重影响的疾病。此外，我们假设这些分子可能受到这样的操纵，使它们能够特异性地针对MC和PBB。为了验证这些假设，我们将使用原始人类MC和PBB的组合，以及包括过敏、关节炎和多发性硬化症在内的人类疾病的小鼠模型。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很大的MC/PBB影响的疾病的诱导和进展。这一全新的研究计划可能不仅为过敏治疗奠定了新的策略，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奠定了基础。 与公共健康相关的肥大细胞是重要的效应细胞，传统上与启动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细胞。我们发现了一种新的机制，通过使用名为富勒烯的纳米材料来抑制过敏过程。这项提议的目标是确定这些分子是否有可能成为治疗MC介导性疾病的可行的新疗法。PHS 398/2590(09/04版，2006年4月4日重新发布)页面续格式页面

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