Functionalized nanoparticles for real time imaging of cerebral lesions

中风患者通常遭受大脑的微缺血性损伤，由于其体积小，最初未被注意到。然而，从长远来看，它们往往会引发不可逆的神经退行性变化，并伴有使人衰弱的并发症，目前尚无治愈方法。在此，我们建议使用发光纳米颗粒或x射线计算机断层扫描（CT）造影剂开发新的实时无创成像方案。我们的方法是独特的，因为它依赖于以下方面的协同作用：(1)材料纳米科学用于成像剂的设计和合成，(2)机械药理学用于成像和临床前研究的部署，以及(3)最先进的医学成像技术，这些技术将由加拿大ART Advanced Research Technologies Inc.公司设计并商业化的仪器提供。总体目标是：1。开发和测试适用于实时、无创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. 利用这些成像工具评估啮齿动物脑卒中模型中缺血性病变的程度；和3。测试临床使用的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“鸡尾酒”药物的新鼻内制剂的有效性。虽然这项研究的目的是为了治疗缺血性病变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，并通过为药物开发和诊断提供快速、敏感和可靠的方法，使加拿大卫生界受益

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