Raman Nanotheranostics - RaNT - developing the targeted diagnostics and therapeutics of the future by combining light and functionalised nanoparticles

人们普遍预计，迅速崛起的“纳米体视学”领域将在未来十年乃至更长时间内对医疗保健产生重大影响。治疗学是治疗和诊断的结合。它的目标是识别疾病并通过单一、有效的非手术程序治疗它们。我们最近开发的金纳米技术使仅用光就能在体内厘米深处测量的癌症等疾病的识别方面具有前所未有的准确性。此外，光还可以用来触发金粒子，以受控、安全和有针对性的方式摧毁使用这种方法确定的疾病细胞或组织。肿瘤疾病将受益于提供早期准确诊断的新方法，以及为每个患者量身定做的有效局部治疗和对治疗过程的非侵入性监测。现有的诊断技术无法测量异常细胞组成的早期变化--当它们仍在体内时，具有足够的准确性或灵敏度。在癌症中，在细胞和组织中发现的分子变化是驱动肿瘤发展的基因突变的下游效应。我们的目标是找到一种新的方法，在不切除组织的情况下识别体内的这些早期变化，并利用它们进行靶向治疗或监测进展，为患者的结果和成本带来切实的好处。我们还将开发一种新的方法来组装微小的金纳米颗粒簇，使其能够有效地光学读出，并安全地通过身体和靶向感兴趣的疾病细胞。这些簇将被包裹在经过验证的生物兼容包裹中，这种包裹增强了跨越生物屏障的运输，并进行了修改，使它们能够选择性地被疾病细胞吸引。最重要的是，我们集合了独特的能力：从许多厘米深处的星团中非侵入性地读出多种信号；建立安全的星团，随着时间的推移(例如几个小时)会自我分解成可以从身体排泄出来的更小的安全单元；调整这些结构的大小和内容，使光能够通过加热或药物输送触发治疗反应；并提供治疗过程中组织内局部温度的实时体内读数，以最大限度地提高其有效性，并将对健康组织的附带损害降至最低。此外，拟议的纳米体感疗法将通过单个纳米结构提供检测和定位许多不同疾病的能力。它利用功能化的金纳米颗粒(通过表面增强的拉曼-SERS)从报告分子中产生特定的光谱特征，这些分子受到来自体外的低强度、安全的近红外激光的照射。这为通过同时瞄准许多特定的分子靶标，在体内实时识别和定位疾病的不同表现开辟了道路。近红外光几乎不会被组织和细胞吸收，而且不会致癌(与紫外线不同)，因此有助于安全、定期、非侵入性地监测治疗或疾病的进展。在不久的将来，患者将根据自己的需要选择有效和有限的治疗方法，以最大限度地发挥必要治疗的治疗价值，并防止应用任何不必要的、可能因副作用而有害的治疗方法。这不仅有可能提高存活率，而且有可能提高那些可能在当前临床系统中获得主要治疗的人的生活质量，并可能每年在英国各地节省大量无效治疗的GB 100毫秒。我们组成了一个由互补研究领域的世界领先专家组成的团队，以促进对未来医疗保健产生影响的一些重大进展。

The rapidly emerging field of 'Nano-Theranostics' is widely expected to have a significant impact on healthcare in the next decade and beyond. Theranostics is the combination of therapy and diagnosis. It aims to identify diseases and treat them in a single, effective non-surgical procedure. Our recently developed gold nano-technologies allow unprecedented accuracy in identifying diseases such as cancers measured at depths of centimetres inside the body using only light. Furthermore, light can then also be used to trigger the gold particles to destroy the diseased cells or tissues identified using this method in a controlled, safe and targeted fashion.Numerous diseases would benefit from new methods to provide early accurate diagnosis, with effective localised treatment tailored to each patient and non-invasive monitoring of treatment progress. Existing diagnostic techniques do not manage to measure the early changes in the makeup of abnormal cells - whilst they are still in the body with sufficient accuracy or sensitivity. In cancers the molecular changes found within the cells and tissues are the downstream effects of genetic mutations driving the tumour development. A novel method to identify these early changes within the body, without removing tissue, and to use them to target treatment or monitor progression is our objective, delivering tangible benefits in patient outcome and costs.We will also develop a novel approach for assembling tiny gold nanoparticle clusters to enable their effective optical readout and to pass safely through the body and target diseased cells of interest. These clusters will be coated in a proven biocompatible wrapping which enhances transport across biological barriers, and modified to enable them to be attracted selectively to diseased cells. Most importantly we bring together the unique capabilities: to read out multiple signals non-invasively from clusters at depths of many cm; to build safe clusters which will self-disintegrate over time (eg hours) into smaller safe units that can be excreted from the body; to tune the size and contents of these constructs to enable light to trigger a therapeutic response, via heating or drug delivery; and to provide real-time in-vivo readout of the local temperature within the tissue during treatment to maximise its effectiveness and minimise collateral damage to healthy tissue.Furthermore, the proposed Nano-Theranostic approach will deliver the ability to detect and localise many different diseases via a single nano-construct. This utilises functionalised gold nanoparticles to produce specific spectroscopic signatures (via surface enhanced Raman - SERS) from reporter molecules illuminated with low intensity, safe, near-infrared laser light from outside the body. This opens the way for real-time identification and localisation, within the body, of distinct expressions of disease, by targeting numerous specific molecular targets simultaneously. The near-infrared light is barely absorbed in tissues and cells and is non-cancerous (unlike UV light), thus facilitating the possibility of safe, regular non-invasive monitoring of treatment or progression of disease.In the near future, patients will have effective and limited treatments selected specifically for their needs, to maximise the therapeutic value of any necessary treatment and prevent the application of any unnecessary, and potentially harmful through side effects, therapy. This has the potential to lead to not only increased survival rates, but increased quality of life for those likely to be offered major treatments in current clinical system and also potentially save many £100Ms across the UK each year on ineffective treatments.We constitute a team of world leading experts in complementary research fields to facilitate a number of significant advances impacting on healthcare of the future.