Investigations into New Chemical Toolkits for Drug Delivery, Sensing and Cellular Imaging Applications using the Fluorescence Labelling of Biomolecule

使用生物分子荧光标记研究用于药物输送、传感和细胞成像应用的新型化学工具包

• 批准号: 2427593
• 金额: --
• 依托单位: University of Bath
• 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: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2427593
• 关键词: Investigations; into; New; Chemical; Toolkits

As healthcare and technology advances lead to longer life expectancies, an ever increasing and ageing populationfaces a growing risk from non-communicable diseases such as cancer. The development of novel, targetedpersonalised sensing and imaging drugs is highly desirable. This research would address cleaner, rapid syntheticprocesses with pharmaceutical relevance by the utilisation of inexpensive protocols and drugs currently underdevelopment for clinical trials, e.g. immune-therapeutics. The work would be fully embedded in the strategic researchdirection of biosensing and imaging/healthcare technology, which could have real impact in early diagnosis of cancerand personalised medicine. The PhD thesis will focus on the general area of biosensing, imagining and therapeuticinnovations for cancer diagnosis and therapy.OutlineThe project would largely be based on enhancing the understanding of the fundamental interactions betweenluminescent probes and targeting biomolecules such as synthetic peptides upon conjugation, leading to a biologicalprobe, which could potentially target living cancer cells under controlled microenvironments. A secondary aim wouldbe to gain an in depth understanding of the synthetic and analytical chemistry underpinning the chemistry implicatedin the antibody labelling or tagging with small fluorescent molecules.We would design, synthesise, and characterise new metal complexes as "all-in-one" imaging probes, centred oncertain antibodies of interest for clinical trials of cancer, such as Avastin or anti-EGFR. Outputs would lead toimproved sensing and bioimaging probes for early cancer diagnosis, including for hypoxic tumours, which arecurrently hard to access for imaging or treatment. This could advance our fundamental understanding of theassociated conjugation chemistry in aqueous environments, including using bioorthogonal and supramolecularassembly protocols, thus allowing for correlation between antibody behaviour post conju gation and its kineticstability, with the metal ions present in the molecular appendages and their speciation in aqueous media.Project Aimsa) Functionalisation of biomolecules of interest for immune-therapies such as simple synthetic peptides, onto metalbound imaging probes.b) Understanding how fluorescent metal complexes can be incorporated in multimodality (PET/optical) probes, whichare then anchored onto antibodies without destroying the fragile biomolecular constructs.c) Labelling of biomolecules with model species of relevance to PET/SPECT metallic radio isotopes such as 68Gaand 89Zr. Development and testing protocols for the "cold" chelation of Zn(II), Ga(III) and Zr(IV) ions in water.Dr Charareh Pourzand (20 %) will assist in this project by providing knowledge and training in tissue and cell culture.This will allow for the imaging probes designed to be tested within cells.Professor Andy Burrows (10 %) will act as a mentor and will also support in the more chemical aspects of this project

随着医疗保健和技术的进步导致寿命更长，人口不断增加和衰老的人口越来越大，癌症等非传染性疾病的风险越来越大。非常需要新颖的，有针对性的感测和成像药物的发展。这项研究将通过利用廉价方案和目前临床试验不发育的廉价方案和药物（例如免疫治疗药。这项工作将完全嵌入生物传感和成像/医疗保健技术的战略研究方向上，这可能会对癌症和个性化医学的早期诊断产生真正的影响。博士学位论文将集中于癌症诊断和治疗的生物传感，想象和治疗性的一般领域。outlinethe项目主要是基于增强对明亮发光探针之间的基本相互作用的理解，而靶向诸如对造成癌症的癌症的生物分子（例如合成肽）的基本相互作用，可能会导致癌症，从而导致癌症，从而使癌症受到癌症的影响，从而使生物癌症受到了癌症的影响，从而使癌症受到了癌症的影响。第二个目的将深入了解化学基础的合成和分析化学，与抗体标记或具有小荧光分子的标记相关。我们将设计，合成并将新金属复合物描述为“全合成”探针的“全合成”探针的“全合成”抗体，对癌症的中心抗体，例如癌症，例如癌症，例如癌症，例如cancer，例如AVAST，例如AVAST，例如AVAST，例如AVAST，例如AVAST。输出将导致早期癌症诊断的Tomed Sensing和生物成像探针，包括缺氧性肿瘤，这些肿瘤难以进入成像或治疗。这可能会推动我们对水性环境中硫其相关的结合化学的基本理解，包括使用生物正交和超分子安装方案，从而允许抗体行为在conju gation后抗体行为及其动态稳定性之间的相关性与其动力学稳定性，其金属离子与分子附加物中的金属相关性以及其在其形式上的形式相关性，以及其形式的媒介媒体，以实现类似的媒体媒体，以实现类似的媒体媒体，以实现类似的媒体媒体，构成了类似的媒介，这些媒体是针对生物的媒介媒体的，即构成了类似的媒介媒体，即构成了类似的媒介，构成了抗体离子的生物元素。对于免疫膜，例如简单的合成肽，将荧光金属复合物在多模峰（PET/光学）探针中纳入荧光金属络合物，然后将其固定在抗体上，而不会破坏脆弱的生物分子结构。锌（II），GA（iii）和Zr（IV）离子的“冷”螯合的开发和测试方案将通过提供组织和细胞培养的知识和培训来帮助该项目。这将允许在Cells和Proment wills.profsesor andy burrows（10％）中进行进一步测试（10％），并允许该项目进行测试（10％）。