Lipids in Cancer - Advanced nanospectroscopic profiling and assessment of non-conventional drugs for cancer therapy

本项目旨在研究拉曼散射及其一些变体(表面增强(SERS)、相干反斯托克斯(CARS)和受刺激(SRS))的使用，以评估常规抗癌药物治疗前后癌细胞和组织中脂质的分布情况，特别是已显示出作为抗癌药物的前景的新的替代药物。拉曼散射是一种强大的振动技术，可以根据特定的分子振动提供细胞和组织的无标记图像。然而，使用拉曼散射对大面积进行成像可能需要相当长的时间，然而，相干反斯托克斯拉曼散射(CARS)和受激拉曼散射(SRS)的发展使图像采集能够非常迅速地进行，通过使用双光子非线性过程来监控单个振动波长，这使得可以在几秒钟内从大面积组织中收集图像。我们可以调谐到脂肪的振动，并产生高度可视化的组织图像。通常，拉曼散射是一个微弱的过程，然而，可以通过使用金属纳米颗粒来改善拉曼散射的不敏感性，金属纳米颗粒可以增强拉曼散射，而且当药物添加到其表面时，也可以用于提供局部和更有效的药物响应。脂质生物合成的变化是癌症生长的一个基本方面，癌症肿瘤中从头合成的脂质合成明显上调。到目前为止，可用于分析脂质的技术要么是破坏性的，例如质谱学，要么需要使用可能严重干扰固有生物过程的笨重的外在标记，例如荧光。在这个项目中，我们建议了解癌症中脂类代谢的改变，以及靶向脂类和脂类合成的药物作为改进和替代癌症治疗的潜在候选药物的作用。更具体地说，我们有兴趣更多地了解胆固醇合成途径，并利用活细胞和组织实时跟踪这一途径。这远远超过了任何其他技术所能达到的当前技术水平。特别是，我们对使用他汀类药物来提高前列腺癌患者对去势反应的理解感兴趣，他汀类药物通常用于治疗心血管疾病。在EPSRC资助的一个项目(EP/L014165/1)中，我们正在研究附着在金属纳米颗粒上的他汀类药物作为改善心脏病治疗药物的作用。这一团队将与CUNY的松井浩史教授合作，他是药物输送方面的专家，利用本提案中详细介绍的方法，开发一种跟踪不同药物/纳米颗粒配方对癌症进展的影响的方法。

This project aims to investigate the use of Raman scattering and some of its variations (surface enhanced (SERS), coherent anti-Stokes (CARS) and stimulated (SRS)) to assess the profiling of lipids in cancer cells and tissue prior to and following treatment with conventional anticancer drugs and particularly new alternative drugs that have shown promise as anticancer agents. Raman scattering is a powerful vibrational technique that can provide label free images of cells and tissue based on specific molecular vibrations. To image large areas using Raman scattering can take considerable time, however, the development of coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS) has enabled image acquisition to take place very rapidly through the use of a two photon non-linear process to monitor a single vibrational wavelength, which allows the collection of images in a matter of seconds from large areas of tissue. We can tune into lipid vibrations and produce highly visual images of tissue. Typically Raman scattering is a weak process, however, the insensitivity of Raman scattering can be improved through the use of metal nanoparticles, which can enhance Raman scattering but also be used to provide localised and more efficacious drug response when drugs are added to their surface.Changes in lipid biosynthesis is a fundamental aspect of cancerous growth, with de novo lipid synthesis markedly upregulated in cancer tumours. To date the technologies available for analysing lipids are either destructive e.g. mass spectrometry or require the use of bulky extrinsic labels that can interfere significantly with innate biological processes e.g. fluorescence. In this project we propose to understand the altered lipid metabolism in cancer, and the role of drugs that target lipids and lipid synthesis as potential candidates for improved and alternative cancer treatment. More specifically we are interested in understanding more about the cholesterol synthesis pathway and following this in real time using live cells and tissue. This is well beyond the current state of the art possible by any other technology. In particular, we are interested in using statins, which are conventionally used to treat cardiovascular disease, as agents to improve understanding of response to castration in prostate cancer patients. In a project funded by the EPSRC (EP/L014165/1), we are investigating the role of statins attached to metallic nanoparticles as improved agents for treatment of heart disease. This studentship will work in partnership with Prof Hiroshi Matsui at CUNY who is an expert in drug delivery to develop a way of following the effect of different drug/nanoparticle formulations on the progression of cancer using the methodology detailed in this proposal.