Functionalized nanoparticles for real time imaging of cerebral lesions

中风患者通常患有微小的脑缺血损伤，由于体积小，最初没有被注意到。然而，从长远来看，它们往往会引发不可逆转的神经退行性变化，并伴随着使人衰弱的并发症，目前还没有找到治愈的方法。我们建议开发新的实时非侵入性成像方案，使用发光纳米颗粒或X射线计算机断层扫描(CT)造影剂。我们的方法是独一无二的，因为它依赖于(I)用于设计和合成显像剂的材料纳米科学，(Ii)用于部署成像和临床前研究的机械药理学，以及(Iii)最先进的医学成像技术，它将由总部设在加拿大的ART Advanced Research Technologies Inc.设计和商业化的仪器提供。总体目标是：1.开发和测试适用于实时、非侵入性成像的新型近红外发射量子点和X射线断层成像造影剂；2.使用这些成像工具来评估啮齿动物中风模型中的缺血性损害的范围；以及3.测试临床上使用的药物NAD+(烟酰胺腺嘌呤二核苷酸)和临床前研究中使用的由米诺环素、利鲁唑和尼莫地平组成的药物“鸡尾酒”的新鼻腔制剂的有效性。虽然拟议的研究旨在研究治疗缺血性损害的药物的临床前筛选方法，但所开发的成像设备和试剂将广泛应用于临床前研究，并通过提供快速、灵敏和可靠的药物开发和诊断方法而造福加拿大健康社区。

Stroke victims commonly suffer micro-ischemic lesions of the brain that initially remain unnoticed due to their small size. In the long term, however, they tend to trigger irreversible neurodegenerative changes accompanied by debilitating complications for which no cure has been found. We propose here to develop new real time non-invasive imaging protocols using luminescent nanoparticles or X-ray computed tomography (CT) contrast agents. Our approach is unique in as much as it relies on the synergy of (i) materials nanoscience for the design and synthesis of imaging agents, (ii) mechanistic pharmacology for the deployment of imaging and pre-clinical studies and (iii) state-of-the-art medical imaging technology, which will be provided by instrumentation designed and commercialized by the Canadian-based company ART Advanced Research Technologies Inc. The overall objectives are: 1. to develop and test novel near IR emitting quantum dots and X-Ray tomography contrast agents suitable for real time, non-invasive 1 imaging; 2. to use these imaging tools to assess the extent of ischemic lesions in rodent stroke models; and 3. to test the effectiveness of new intranasal formulations of either NAD+ (Nicotinamide adenine dinucleotide), a drug in clinical use clinically, and of a drug "cocktail", composed of minocycline, riluzole and nimodipine, used in pre-clinical investigations. While the research proposed is aimed towards preclinical screening methods for drugs in the treatment of ischemic lesions, the imaging devices and agents developed will be widely applicable in pre-clinical research and benefit the Canadian health community by providing fast, sensitive, and reliable methods in drug development and diagnostics