Development of lanthanide probes for the monitoring of pH and the physiological redox environment.

开发用于监测 pH 值和生理氧化还原环境的镧系元素探针。

• 批准号: 2285033
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2285033
• 关键词: Development; lanthanide; probes; monitoring; pH

This project involves the preparation and study of a series of metal complexes that respond to changes in the biological chemistry of living systems, with a particular focus on preparing complexes that respond to the biochemical consequences of redox stress in biology. There are several conditions which affect the pH and redox environment within the body these include cancer1,2, chronic inflammation1, ischemia1 and Alzheimer's disease2. Multimodal lanthanide probes could be made to detect tissue being starved of oxygen (hypoxia) and tissue damage by reperfusion (the restoration of blood flow and, therefore, the supply of oxygen to areas to which blood flow has been restricted) as both these conditions cause the pH3 and redox environment of the cells involved to become unbalanced. Lanthanide probes are lanthanide complexes which have been tailored to respond to the chemical environment around them. Their response can be observed by magnetic resonance imaging (MRI), fluorescence imaging and many other imaging techniques. The development of multimodal probes which react to these imbalances could be used to effectively monitor and diagnose these and many other conditions by MRI and fluorescence imaging. The aim of this project is to produce multimodal lanthanide probes to monitor and detect physiological conditions by MRI, fluorescence imaging and other imaging techniques. We hope to achieve this by modifying kinetically stable lanthanide complexes by adding redox, pH, and enzyme sensitive functional groups The project explores a new methodology to achieve these goals, relying on the exploitation of a modular route to heterometallic complexes to incorporate two luminescent domains that enable changes in guest concentration to be quantified. This project falls within the EPSRC manufacturing the future, healthcare technologies and medical imaging (including medical image and vision computing) research area as it concerns the production and multimodal probes to be used for medical imaging for the diagnosis of a number of conditions and imbalances.

该项目涉及一系列金属络合物的制备和研究，这些金属复合物应对生物化学系统的生物化学变化，特别着重于制备对生物学中氧化还原胁迫的生化后果响应的复合物。有几种影响体内pH和氧化还原环境的情况包括癌症1,2，慢性炎症1，缺血1和阿尔茨海默氏病2。可以做出多模式灯笼探针，以检测组织的氧气（缺氧）和通过再灌注（恢复血流的恢复，因此，氧气供应血液流量已受到限制的区域的供应），因为这两种情况都会导致涉及细胞的pH3环境，并导致氧气供应变得不平衡。灯笼探针是针对周围化学环境响应的灯笼型复合物。可以通过磁共振成像（MRI），荧光成像和许多其他成像技术观察到它们的响应。对这些失衡反应的多模式探针的发展可用于通过MRI和荧光成像有效监测和诊断这些条件和许多其他条件。该项目的目的是生产多模式的灯笼探针，以通过MRI，荧光成像和其他成像技术来监测和检测生理条件。我们希望通过添加氧化还原，pH和酶敏感的官能团来修饰动力学稳定的灯笼型络合物，该项目探索了一种新方法来实现这些目标，依靠将模块化途径剥削到异质金属配合物中，以纳入两个发光域，以纳入两种光度域，从而使宾客浓度变化以量化来量化宾客浓度。该项目属于EPSRC制造的未来，医疗保健技术和医学成像（包括医疗图像和视觉计算）研究领域，因为它涉及用于诊断多种疾病和失衡的医学成像的生产和多模式探针。