Luminescent/PET-active quantum dots for multimodal imaging of prostate cancer

PHD项目的目标：基于无镉结构制造新的发光量子点。将F-18配位到结构的表面，使其既具有PET活性又具有发光活性。将该结构用于前列腺癌的光学成像和PET成像。项目描述：前列腺癌(PC)每年影响英国约47,700名男性。在英国，这是最常见的癌症，75岁以上的S中有35%患有PC。经过积极的监测和监测(MRI、PSA和活检)，目前的主要临床治疗方法之一是手术(机器人辅助的根治性前列腺癌切除术)，然而，由于原发肿瘤通常难以在前列腺内划定，35%的患者将有阳性的肿瘤边缘(即不是所有的肿瘤都被切除)。这需要辅助治疗，例如，放射治疗的并发症风险较高，治愈机会较低。需要一种新的显像剂专门结合到肿瘤上，准确地勾勒出肿瘤的边界，从而为外科医生提供更直接的可见细节，并能够在机器人前列腺切除术中切除所有癌症，以防止未来的复发和进一步的侵入性治疗。新的显像剂正在出现，具有多模式功能，允许在不同尺度长度和不同组织深度进行疾病状态成像，从而实现更快、更准确的诊断。量子点是细胞成像的首选纳米材料，具有明亮、稳定和可调谐的发射，与传统的有机染料相比具有许多优点。然而，这些粒子只提供光学发射作为一种成像能力，这意味着其他强大和互补的技术被忽略了。在这个项目中，我们将开发一种基于磷化铟(InP)的无重金属量子点系统，其固有的稳定发射可在可见光谱范围内调节。这些微粒的好处是被认为是不含重金属的，传统的含镉材料是在常规医院和临床环境中实现QD应用的主要障碍。目前，基于InP的生物显像剂开始出现在市场上，InP基材料的一个主要优势是它们与氟的配位作用，它可以填充表面缺陷，增强量子点发射。这种表面刻蚀被认为是改善InP量子点光学性质的关键方法。在这个项目中，我们将使用放射性核素F-18来配位到基于InP的量子点的表面，为我们提供用于成像的发光和PET活性材料。随着F-18衰变为氧气，最终材料将是一种具有受控表面氧化层的材料，这也被视为稳定发光量子点的关键成分。因此，我们不仅有一个多模式的量子点系统，而且还使用放射性元素作为一种可控的表面工程方法。我们还将通过将材料与锌合金化并沉积一层硫化锌外壳来探索粒子的结构，以期在保持PET活性的同时提高发射轮廓。这些颗粒将用于光学显微镜和正电子发射计算机断层扫描对各种疾病状态进行成像。这个项目将适合对生物成像感兴趣的合成无机化学家。

Aim of the PhD Project:To manufacture new luminescent quantum dots based on cadmium-free structures.To coordinate F-18 to the surface of the structures, making them both PET-active and luminescent.To use structures in optical imaging and PET imaging of prostrate cancer.Project Description:Prostate cancer (PC) affects around 47,700 men in the UK each year. In men, it is the most common cancer in the UK with 35% of over 75's having PC. After active monitoring and surveillance (MRI, PSA and biopsies), one of the current primary clinical treatments is surgery (robot-assisted radical prostatectomy) However, as the primary tumour is often difficult to delineate within the prostate gland, 35% of patients will have a positive tumour margin (i.e. not all of the tumour is resected). This requires adjuvant treatment, e.g. radiotherapy with higher risks of complications and lower chance of cure. A new imaging agent is needed that binds specifically to the tumour, to give accurate delineation of the tumour boundaries, therefore providing the surgeon with more direct visible detail and the ability to remove all of the cancer during robotic prostatectomy, to prevent future reoccurrence and further invasive therapy.New imaging agents are emerging with multimodal capabilities, allowing imaging of disease states at different scale lengths and different tissue depths, resulting in quicker and more accurate diagnoses. Quantum dots (QDs) have emerged as the premier nanomaterial for cellular imaging, having bright, stable and tuneable emission, offering numerous benefits over traditional organic dyes. The particles, however, only offer optical emission as an imaging capability which means other, powerful and complimentary techniques are over-looked.In this project, we will develop a heavy metal-free quantum dot system based on indium phosphide (InP), with inherent stable emission tuneable over the visible spectrum. These particles have the benefit of being considered 'heavy metal-free', with classical cadmium containing materials presenting a major hindrance in realising QD applications in routine hospital and clinical settings. Currently, InP based biological imaging agents are beginning to emerge on the market.A major advantage of InP-based materials is their coordination with fluorine, which fills surface defects and enhances QD emission. This surface etching is considered a key method for improving the optical properties of InP QDs. In this project, we will use the radionuclide F-18 to coordinate to the surface of InP-based QDs providing us with luminescent and PET active materials to be used in imaging. As F-18 decays to oxygen, the final material will be a material with a controlled surface oxide layer, also seen as key component to stable luminescent quantum dots. We therefore not only have a multimodal QD system, but also use the radioactive element as a method for controllably engineering the surface.We will also explore the structure of the particle by alloying the material with zinc and depositing a ZnS shell with a view to enhancing the emissive profiles, whilst maintaining PET activity. These particles will be used in imaging various disease states with both optical microscopy and PET scans. This project would suit a synthetic inorganic chemist with an interest in biological imaging.