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

光声成像是一种无创成像技术，结合了超声成像的空间分辨率和深度穿透与光学成像的高对比度和特异性。它的工作原理是用脉冲激光照射造影剂，产生超声波来创建三维图像。该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infraluciferin/荧光素酶连接的金纳米颗粒，用于评估颗粒细胞内化和递送。将通过高分辨率光声成像评估颗粒位置。而红外荧光素将通过激活生物发光来验证细胞内化。学生将合成红外荧光素和氨基-红外荧光素衍生物，这些衍生物连接到活性接头上，用于与金表面上的活性接头偶联。接头可以连接到红外荧光素的任一末端，并且将易于通过一系列酶切割机制降解。使用已经证明用于NP的生物缀合的一系列文献技术，将荧光素-接头缀合物和内切酶附加到适当官能化的Au NP上。然后将测试红外荧光素-Au NP和黄原胶酶-Au NP的体外切割。可能需要对接头进行改进，以最终证明体内方法、切割和光声成像。通过使用近红外生物发光来精确定位造影剂的改进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。该项目福尔斯EPSRC的研究主题：物理科学和医疗保健技术。合成有机化学的EPSRC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的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.