Spectroscopic analysis of single nanoparticles for drug delivery

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效益，并且是所有主要制药公司大量研究的主题。例如，涉及高毒性药剂的癌症治疗可以比使用标准配方更精确地针对肿瘤，大大减少总剂量和由此产生的副作用，并且可以将基于遗传物质的疫苗加载到病毒载体中，以刺激细胞中的免疫反应并增加治疗效果。然而，流体悬浮液中纳米颗粒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发展，并降低临床吸收新纳米药物的障碍。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尤其强大，因为它们以可管理的形式提供了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装置表征流体中单个纳米颗粒的工作的基础上。具体而言，该项目将研究通过光学镊子对捕获在微腔中的纳米粒子进行增强拉曼光谱的程度。我们希望在项目中探索两种不同的方法，基于共振腔增强激发场和增强拉曼散射场。前一种方法有望减少背景信号，并允许对装载的药物质量进行无需校准的测量，而后一种方法有望允许研究更小的颗粒并提供更高的信噪比。该方法将涉及具有必要反射率光谱的微腔镜的设计和工程，流动池内微腔的构建（这是对现有设备的改编）以及具有高灵敏度的合适光收集系统的构建，包括低噪声光谱仪和单光子探测设备。然后，该项目将包括通过表征测试样品来演示该技术，从简单的纳米颗粒开始，如固体二氧化硅，它显示出强烈而明确的拉曼特征，然后转向带有或不带有附加化学物质的介孔颗粒。该项目由牛津高q有限公司支持，该公司提供CASE充值资金。Oxford HighQ Ltd是从该研究小组分拆出来的，开发用于纳米医学研究和其他微腔增强传感应用的商业仪器。该公司的总部设在贝格布罗克科学园，从大学实验室到那里有定期的班车服务。通过工业主管，首席技术官Aurelien Trichet博士，该公司将提供关于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联系以获取样品，以及为项目产出的商业化提供潜在途径。该项目属于EPSRC医疗保健技术主题。

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.