Infralucifern/luciferase gold nanorod conjugates for NIR bi-modal imaging

光声成像是一种将超声成像的空间分辨率和深度穿透性与光学成像的高对比度和特异性相结合的非侵入性成像技术。它的工作原理是用脉冲激光照射造影剂，脉冲激光产生超声波，产生三维图像。这项技术的一个问题是验证造影剂的细胞位置。该项目旨在开发一系列与次铝红素/荧光素酶相连的金纳米颗粒，用于评估颗粒细胞的内化和传递。粒子位置将通过高分辨率光声成像进行评估。学生将通过激活生物发光来验证细胞内化。学生将合成次生红素和氨基次生红素衍生物，连接到活性连接物，然后连接到金表面的活性连接物。连接体可以连接到次生红素的两端，并通过一系列的酶切割机制容易降解。次生荧光素-连接物和荧光素酶将被添加到适当功能化的金纳米颗粒上，使用一系列已经被证明用于纳米颗粒生物结合的文献技术。然后将在体外测试次生荧光素-Au纳米颗粒和荧光素酶-Au纳米颗粒的切割情况。为了最终证明该方法在活体、切割和光声成像中的应用，可能需要对连接子进行改进。通过使用近红外生物发光技术来改进对比剂的精确度，将导致成像技术的改进，供各地的成像科学家使用，以更有效地研究疾病。该项目属于EPSRC的研究主题：物理科学和医疗技术。EPSRC合成有机化学研究领域将使该项目能够在化学生物学和生物化学以及医学成像等其他研究领域提供实际应用。

Photoacoustic imaging is a non-invasive imaging technique, combining the spatial resolution and deep penetration of ultrasound imaging with the high contrast and specificity of optical imaging. It works by irradiating a contrasting agent with pulsed laser light which generates an ultrasound to create three dimensional images. One problem the technique has is verifying the cellular location of the contrast agent. The project aims to develop a series of gold nano particles linked to infraluciferin/luciferase for assessing particle cell internalisation and delivery. Particle location will be assessed by high resolution photoacoustic imaging. Whereas, infraluciferin will verify cell internalisation by activating bioluminescence.The student will synthesise infraluciferin and amino-infraluciferin derivatives linked to an active linker for coupling to an active linker on a gold surface. The linker can be attached to either end of infraluciferin and will be susceptible to degradation through a range of enzyme cleavage mechanisms. The infraluciferin-linker conjugate and luciferases will be appended to suitably functionalised Au NPs using a range of literature techniques already proven for the bioconjugation of NPs. The infraluciferin-Au NPs and luciferase-Au NPs will then be tested for cleavage in vitro. Refinements of the linker may be required to ultimately demonstrate the method in vivo, cleavage and photoacoustic imaging. The improvement in the pinpointing of contrasting agents through using NIR bioluminescence will lead to improved imaging techniques for use by imaging scientists everywhere to study disease more effectively.The project falls within the EPSRC research themes: Physical Sciences and Healthcare Technologies. The EPSRC research area of Synthetic Organic Chemistry will enable the project to deliver practical applications in the other research areas of Chemical Biology and Biological Chemistry, and Medical Imaging.