Design and Development of Functional Nanoparticles as Contrast Agents for Magnetic Resonance Imaging (MRI).

目的：设计和开发纳米材料作为多功能靶向治疗和诊断剂。这包括生产比报告的类似物具有增强MR成像能力的造影剂、刺激响应剂和研究用于增强MR对比度的新平台。此外，质子弛豫的基本机制将被调查的介孔二氧化硅纳米粒子（MSNs）掺杂Dy 3 +.Description和潜在的影响：纳米技术被定义为与至少一个尺寸在纳米范围（1-100 nm）的材料的研究。由于纳米尺寸，纳米材料具有提供改进的物理、化学或生物特性的能力，与分子类似物相比具有广泛的化学可调性和更高的表面积与体积比，从而允许更好地操纵物质。纳米技术的一个应用是使用纳米材料作为MRI的造影剂。可以通过使用刺激响应颗粒来实现丰富的诊断能力，其中水对MR活性顺磁螯合物的访问是可逆门控的，从而打开/关闭对比能力。这使得一个显着的变化，在一个特定的病理区域内的对比度differential.Within这个项目中，一个新的胶束平台将被调查。通过研究不同的单体、链转移剂和不同的链长，可以比较对比能力。改变该平台的范围是无限的，能够引入对疾病特异性诊断至关重要的刺激响应性，例如用于癌组织的pH响应剂。除了他的工作外，还将研究掺杂顺磁性Dy 3+的MSN。通过调整Dy 3+的负载密度和优化产生的T2对比度，可以进一步探索居里对弛豫率的依赖性。具有改善的生物相容性、在疾病特异性微环境内的对比度开关“打开”和比当前临床类似物更好的性能的MRI对比剂的生产将是监测疾病进展和对治疗的反应的方式中的宝贵资产。这些目标构成了该项目的主要焦点，希望方法和结果在MRI诊断中真正具有影响力。研究方法的新奇：具有增强对比度能力（包括刺激响应特性）的新型MRI探头的设计、开发和表征。进一步了解对比度增强的原理和控制因素。与EPSRC的战略和研究领域保持一致：本项目涵盖了EPSRC的几个研究领域。MRI活性纳米材料系统的生产作为潜在的造影剂，提供非侵入性和改善的诊断福尔斯属于医疗保健技术的职权范围。此外，该项目还涵盖了面向未来的制造，因为刺激响应系统可用于增强对多种疾病的诊断，例如癌组织中存在pH值偏差。最后，该项目福尔斯EPSRC物理科学研究领域，因为理论和方法来自化学的几个分支。

Aims: To design and develop nanomaterials as multifunctional targeted therapeutic and diagnostic agents. This includes the production of contrast agents with enhanced MR imaging capabilities than reported analogues, stimuli-responsive agents and investigation of new platforms for enhancing MR contrast. In addition, the underlying mechanism of proton relaxation will be investigated for mesoporous silica manoparticles (MSNs) doped with Dy3+.Description and Potential Impact: Nanotechnology is defined as the study of materials with at least one dimension in the nanometre range (1-100 nm). Due to nanometric sizes, nanomaterials have the ability to offer improved physical, chemical or biological properties, with a wide ranging chemical tunability and higher surface area-to-volume ratio over molecular analogues allowing for greater manipulation of matter. One application of nanotechnology is the use of nanomaterials as contrast agents for MRI. Enriched diagnostic capabilities can be achieved via the use of stimuli-responsive particles where water access to the MR active paramagnetic chelate is reversibly gated, switching the contrast capabilities on/off. This allows for a significant change in the contrast differential within a particular pathological region.Within this project a novel micellular platform will be investigated. By investigating different monomers, chain transfer agents, and different chain lengths the contrast capabilities can be compared. The scope to alter this platform is endless, with the ability to introduce stimuli-responsivity vital for disease specific diagnosis e.g. pH-responsive agents for cancerous tissue. In addition to his work, MSNs doped with paramagnetic Dy3+ will also be studied. By tuning the loading density of Dy3+ and optimising the generated T2 contrast the Curie dependence on relaxivity can be further explored. The production of a MRI contrast agent with improved biocompatibility, a contrast switch 'on' within a disease-specific microenvironment and greater performance than current clinical analogues would be an invaluable asset in the way disease progression and response to treatment is monitored. These aims form the main focus of this project, with the hope that the methods and results will be truly impactful in MRI diagnostics. Novelty of the Research Methodology: The design, development and characterisation of new MRI probes with enhanced contrast capabilities, including stimuli-responsive properties. Further understanding of the theory behind contrast enhancement and the controlling factors. Alignment to EPSRC's Strategies and Research Areas: Several EPSRC research areas are encompassed in this project. The production of MRI active nanomaterial systems as potential contrast agents providing non-invasive and improved diagnosis falls under the remit of Healthcare Technologies. In addition, the project covers Manufacturing for the Future since stimuli-responsive systems are applicable for an enhanced diagnosis of a plethora of diseases, e.g. deviations in pH are present within cancerous tissue. Finally, the project falls within the EPSRC Physical Sciences research area since the theory and methods stem from several branches of Chemistry.