Spectroscopic analysis of single nanoparticles for drug delivery

用于药物输送的单个纳米颗粒的光谱分析

• 批准号: 2385510
• 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: 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-2385510
• 关键词: Spectroscopic; analysis; single; nanoparticles; drug

The use of nanoparticles as vehicles for targeted drug delivery offers significant clinical benefits and is the subject of considerable research by all of the major pharmaceutical companies. For example cancer therapies involving highly toxic agents can be targeted at tumours much more precisely than is possible using standard formulations, greatly reducing the overall dose and resultant side-effects, and vaccines based on genetic materials can be loaded into viral vectors to stimulate the immune response in cells and increase therapeutic benefit. The detailed study of drug loading and release by nanoparticles in fluid suspension is an outstanding challenge however, and new measurements techniques are required to advance the development of drug delivery nanomaterials and to lower the barriers to clinical uptake of new nanomedicines. Techniques that allow quantitative and chemically specific measurement of single nanoparticles in solution are particularly powerful in this regard as they give the clearest picture of the composition of the particles in an administrable form.This project will build on the group's previous work on the characterisation of single nanoparticles in fluids using optical microcavity devices. Specifically the project will investigate the degree to which enhanced Raman spectroscopy can be performed on nanoparticles trapped in the microcavities by optical tweezing. There are two different approaches that we hope to explore during the project, based on resonant cavity enhancement of the excitation field and enhancement of the Raman scattered field. The former approach is expected to reduce background signals and allow for calibration-free measurement of the mass of drugs loaded, while the latter approach is expected to allow the study of smaller particles and provide a higher signal-to-noise ratio. The methodology will involve the design and engineering of microcavity mirrors which have the necessary reflectivity spectrum, the construction of the microcavities inside a flow cell (this is an adaptation of existing apparatus) and the construction of a suitable light collection system with high sensitivity, including a low noise spectrograph and single photon detection apparatus. The project will then involve the demonstration of the technique by characterising test samples, starting with simple nanoparticles such as solid silica, which show strong and well-defined Raman signatures, and later moving on to mesoporous particles with and without additional chemical species loaded into them.The project is supported by Oxford HighQ Ltd who provide CASE top-up funding. Oxford HighQ Ltd are a spin-out from the research group, developing commercial instruments for nanomedicine research and other microcavity-enhanced sensing applications. The company is based at the Begbroke Science Park, to which there is a regular shuttle-bus service from the university laboratory. Through the industrial supervisor, CTO Dr Aurelien Trichet, the company will provide advice regarding unmet need in the field of nanoparticle characterisation and links with nanomedicine research groups for accessing samples, as well as offering a potential route for commercialisation of project outputs.This project falls within the EPSRC Healthcare Technologies Theme.

使用纳米颗粒作为靶向药物递送的载体提供了显著的临床益处，并且是所有主要制药公司进行大量研究的主题。例如，涉及高毒性药剂的癌症疗法可以比使用标准制剂更精确地靶向肿瘤，大大降低了总剂量和由此产生的副作用，基于遗传物质的疫苗可以装载到病毒载体中，以刺激细胞中的免疫反应并增加治疗效果。然而，通过纳米颗粒在流体悬浮液中的药物装载和释放的详细研究是一个突出的挑战，并且需要新的测量技术来推进药物递送纳米材料的开发并降低新纳米药物的临床吸收的障碍。在这方面，允许对溶液中的单个纳米颗粒进行定量和化学特异性测量的技术特别强大，因为它们可以提供可管理形式的颗粒组成的最清晰图像。该项目将建立在该小组先前使用光学微腔设备表征流体中单个纳米颗粒的工作基础上。具体而言，该项目将调查在何种程度上增强拉曼光谱可以在微腔中捕获的纳米粒子的光学镊子。我们希望在这个项目中探索两种不同的方法，基于激发场的谐振腔增强和拉曼散射场的增强。前一种方法预计将减少背景信号，并允许装载的药物的质量的无校准测量，而后一种方法预计将允许更小的颗粒的研究，并提供更高的信噪比。该方法将涉及具有必要的反射率光谱的微腔镜的设计和工程，流动池内的微腔的构造（这是现有设备的适应）和具有高灵敏度的合适的光收集系统的构造，包括低噪声光谱仪和单光子检测设备。然后，该项目将通过表征测试样品来演示该技术，从简单的纳米颗粒（如固体二氧化硅）开始，这些纳米颗粒显示出强烈且明确的拉曼特征，然后再转移到介孔颗粒，其中包含或不包含额外的化学物质。该项目由提供CASE补充资金的Oxford HighQ Ltd支持。Oxford HighQ Ltd是该研究小组的一个分支，为纳米医学研究和其他微腔增强传感应用开发商业仪器。该公司位于Begbroke科学园，从大学实验室有定期穿梭巴士服务。通过工业主管，首席技术官Aurelien Trichet博士，该公司将提供有关纳米颗粒表征领域未满足需求的建议，并与纳米医学研究小组建立联系以获取样品，以及为项目输出的商业化提供潜在途径。该项目福尔斯属于EPSRC医疗保健技术主题。