Multi-functional Metal-containing Probes for Brain Imaging

用于脑成像的多功能含金属探针

• 批准号: 2434687
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2434687
• 关键词: Multi; functional; Metal; containing; Probes

The blood-brain barrier (BBB) is the main obstacle to the development of a cure for more than a million people afflicted by neurological disorders and brain cancers in the UK. Entire classes of drugs that have successfully treated diseases in other organs cannot be used in the brain, because they cannot cross the BBB. In recent years, the use of focused ultrasound and microbubbles has emerged as a technique that could finally allow the delivery of such drugs across the BBB and into the brain.Yet despite its potential in the treatment of cancer, current ultrasound drug delivery technologies are too unsafe and deliver too low of a dose to be useful for brain diseases, such as Alzheimer's and Parkinson's disease. We have recently shown, that these limitations cannot be overcome using the conventional sequences used to disrupt the BBB. In such sequences, a long ultrasound pulse is emitted at a slow rate. Each pulse drives the microbubbles flowing through the vasculature into a diverse array of mechanical stimuli. While some of the stimuli produce safe drug delivery events, most of the stimuli produce unwanted damage and toxicity, such as microvascular rupture, arterial damage, and the release of toxic blood-derived proteins into the brain. In this project, we will utilise short pulse sequences within focussed ultrasound to deliver small molecules for imaging and therapy to the brain, alongside peptide-assisted delivery methodology through the BBB.Molecular imaging methods, including magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging, represent promising approaches to overcoming this challenge. The project will focus on the design of functionalised and targeted transition metal- and lanthanide-containing compounds, initially designed for MRI and optical imaging techniques, with radiochemistry being a medium term feature of the project. The focussed ultrasound methodology will be carried out in collaboration with Dr. James Choi in Bioengineering, Imperial College and collaborators in Hong Kong will assist with biological assays and analysis of stapled peptides for brain cancer imaging and therapy.

在英国，血脑屏障(BBB)是治疗100多万神经疾病和脑癌患者的主要障碍。所有成功治疗其他器官疾病的药物都不能在大脑中使用，因为它们不能越过血脑屏障。近年来，聚焦超声和微泡的使用已经成为一种最终可能允许此类药物通过血脑屏障进入大脑的技术。然而，尽管在癌症治疗中具有潜力，目前的超声波药物传递技术太不安全，提供的剂量太低，对阿尔茨海默氏症和帕金森氏症等脑部疾病没有用。我们最近已经证明，使用用于干扰血脑屏障的常规序列不能克服这些限制。在这样的序列中，以较慢的速率发射长的超声脉冲。每个脉冲驱动流经血管系统的微泡进入不同的机械刺激阵列。虽然有些刺激物会产生安全的药物输送事件，但大多数刺激物会产生不必要的损害和毒性，如微血管破裂、动脉损伤和有毒的血源性蛋白释放到大脑中。在这个项目中，我们将利用聚焦超声中的短脉冲序列将小分子用于成像和治疗，并通过BBB提供多肽辅助传递方法。分子成像方法，包括磁共振成像(MRI)、正电子发射断层扫描(PET)、单光子发射计算机断层扫描(SPECT)和光学成像，是克服这一挑战的有希望的方法。该项目将侧重于设计功能化和有针对性的过渡金属和稀土化合物，最初是为核磁共振和光学成像技术设计的，放射化学是该项目的中期特征。聚焦超声方法将与帝国理工学院生物工程专业的James Choi博士合作进行，香港的合作者将协助进行生物分析和分析用于脑癌成像和治疗的装订多肽。