Fluorescence Lifetime Imaging of New Functional Biomaterials for Non Invasive Early Tumour Diagnosis

肿瘤转移前的早期诊断和治疗对患者的生存有重要影响。该项目将展示新型发光光学成像剂，这些成像剂可以导致对癌症的安全、极其准确、非侵入性和负担得起的早期诊断，这些癌症由于光线对消化道等组织的穿透有限而难以非侵入性地获得。我们的RCAH-MGU-Bath合作将利用我们在化学、生物物理和体外和体内生物成像方面的联合专业知识来开发独特的纳米材料。我们将在近红外发光纳米颗粒(在Bath合成，也可以通过项目合作伙伴Intrinsiq材料有限公司获得的纳米颗粒)上附着肿瘤靶向肽和用于癌细胞标志物的商用抗体(ABCAM)。这些结合物将在Bath和RCAH进行研究，用于选择性地向癌细胞传递、摄取、毒性、体外和体内光学成像，使用多光子荧光成像、寿命成像和体内生物发光。我们将与我们的项目合作伙伴(Abcam Plc、Intrinsiq材料有限公司和尼康生物成像英国公司)共同开发纳米颗粒的设计和测试集成技术，以吸引投资通过新型成像试剂进行早期癌症诊断。这将为验证这项技术提供机会，使我们能够在项目完成后进入33亿美元的医疗诊断市场。结果还将出现对纳米粒子与癌细胞之间相互作用的更深入了解，并对其化学生物学进行全面调查，这对提供新的、市场上可用的诊断工具至关重要。最先进的技术依赖于使用有机分子作为显像剂，这些分子通常存在发射寿命短、光稳定性差的问题，或者使用量子点，这是成本高昂和具有生物毒性的。我们将开展第一个毒性基准研究、体外靶向癌细胞和体内生物发光成像。该项目将作为合成化学家、成像技术专家、化学生物学家和细胞生物学家密切合作的结果交付成像探测器。我们将展示由多肽和抗体功能化的近红外发射纳米颗粒(NPs)可以通过克服现有荧光团(如量子点(成本和毒性)和有机荧光团(寿命短)的缺点而应用于医疗诊断市场。该项目可以为解决未来内窥镜未得到满足的临床需求铺平道路，这些内窥镜在近红外系统中运行，并适用于绕过组织自发荧光。它还可以导致在未来的发展中与巴斯生物传感网络的同事以及巴斯癌症研究网络的临床合作者一起开发新的医疗诊断工具。

Early diagnosis and treatment of cancer prior to metastasis has a significant impact on patient survival. This project will demonstrate novel luminescent optical imaging agents that could lead to safe, extremely accurate, non-invasive and affordable early diagnostics of cancers which are difficult to access non-invasively due to limited light penetration through tissues such as the alimentary tract. Our RCaH-MGU-Bath collaboration will utilize our joint expertise in chemistry, biophysics and bioimaging in vitro and in vivo to exploit unique nanomaterials. We will attach tumour targeting peptides and commercial antibodies for cancer cell markers (Abcam) to near-infrared emitting luminescent nanoparticles (synthesised at Bath and also those available via the project partner, Intrinsiq Materials Ltd). These conjugates will be investigated at Bath and at the RCaH for selective delivery to cancer cells, uptake, toxicity, in vitro and in vivo optical imaging using multiphoton fluorescence imaging, lifetime imaging and in vivo bioluminescence. Jointly with our project partners (Abcam Plc, Intrinsiq Materials Ltd and Nikon Bioimaging UK) we will develop a design and testing integrated technology for the nanoparticles to attract investment for early cancer diagnostic by novel imaging agents. This will open up an opportunity to validate this technology which will allow us to tap into the $3.3 billion medical diagnostics market upon completion of the project. A deeper understanding of interactions between nanoparticles and cancer cells and a full investigation into their chemical biology will also emerge as a result, which is crucial to the delivery of new, marketable, diagnostic tools.The state-of-the-art relies on the use of organic molecules as imaging agents that normally suffer from short emission lifetime and poor photostability or use of quantum dots, which are of high cost and biologically toxic. We will carry out the first benchmark study of toxicity, in vitro targeting of cancer cells and in vivo bioluminescence imaging. This project will deliver the imaging probe as a result of the close collaboration between synthetic chemists, imaging technologist, chemical biologists and cell biologists. We will demonstrate that near-IR emitting nanoparticles (NPs), functionalized with peptides and antibodies can be applied to the medical diagnostics market by overcoming disadvantages of existing fluorophores e.g. quantum dots (cost and toxicity) and organic fluorophores (short life span). This project can pave the way to address the unmet clinical need for future endoscopes operating in the NIR regime and adapted to bypass tissue autofluorescence. It can also lead to the development of new medical diagnostic tools in future developments with colleagues in the Biosensing Network at Bath and with the clinical collaborators from the Cancer Research at Bath network.