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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Special Emphasis Panel (ZRG1-BST-M (50))
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Lewis, Catherine D
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Luna Innovations, Inc.
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Dellinger, Anthony L; Zhou, Zhiguo; Kepley, Christopher L (2014) A steroid-mimicking nanomaterial that mediates inhibition of human lung mast cell responses. Nanomedicine 10:1185-93
Dellinger, Anthony; Olson, John; Link, Kerry et al. (2013) Functionalization of gadolinium metallofullerenes for detecting atherosclerotic plaque lesions by cardiovascular magnetic resonance. J Cardiovasc Magn Reson 15:7
Adiseshaiah, Pavan; Dellinger, Anthony; MacFarland, Darren et al. (2013) A novel gadolinium-based trimetasphere metallofullerene for application as a magnetic resonance imaging contrast agent. Invest Radiol 48:745-54
Dellinger, Anthony; Zhou, Zhiguo; Connor, James et al. (2013) Application of fullerenes in nanomedicine: an update. Nanomedicine (Lond) 8:1191-208
Norton, Sarah K; Wijesinghe, Dayanjan S; Dellinger, Anthony et al. (2012) Epoxyeicosatrienoic acids are involved in the C(70) fullerene derivative-induced control of allergic asthma. J Allergy Clin Immunol 130:761-769.e2
Ehrich, Marion; Van Tassell, Roger; Li, Yunbo et al. (2011) Fullerene antioxidants decrease organophosphate-induced acetylcholinesterase inhibition in vitro. Toxicol In Vitro 25:301-7
Nigrovic, Peter A; Malbec, Odile; Lu, Bao et al. (2010) C5a receptor enables participation of mast cells in immune complex arthritis independently of Fc? receptor modulation. Arthritis Rheum 62:3322-33
Norton, Sarah K; Dellinger, Anthony; Zhou, Zhiguo et al. (2010) A new class of human mast cell and peripheral blood basophil stabilizers that differentially control allergic mediator release. Clin Transl Sci 3:158-69
Zhou, Zhiguo; Joslin, Steve; Dellinger, Anthony et al. (2010) A novel class of compounds with cutaneous wound healing properties. J Biomed Nanotechnol 6:605-11
Zhou, Zhiguo; Lenk, Robert P; Dellinger, Anthony et al. (2010) Liposomal formulation of amphiphilic fullerene antioxidants. Bioconjug Chem 21:1656-61

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