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

人们普遍预计，迅速兴起的“纳米治疗诊断学”领域将在未来十年及以后对医疗保健产生重大影响。治疗诊断学是治疗和诊断的结合。它的目的是确定疾病和治疗他们在一个单一的，有效的非手术程序。我们最近开发的黄金纳米技术可以在识别疾病方面实现前所未有的准确性，例如仅使用光在体内厘米深处测量的癌症。此外，光也可以用来触发金粒子，以可控、安全和有针对性的方式破坏使用这种方法识别的病变细胞或组织。许多疾病将受益于提供早期准确诊断的新方法，为每位患者量身定制有效的局部治疗，并对治疗过程进行非侵入性监测。现有的诊断技术无法以足够的准确性或灵敏度测量异常细胞组成的早期变化-而它们仍然在体内。在癌症中，细胞和组织内发现的分子变化是驱动肿瘤发展的基因突变的下游效应。我们的目标是开发一种新方法，在不切除组织的情况下识别体内的这些早期变化，并将其用于靶向治疗或监测进展，从而在患者结局和成本方面带来切实的好处。我们还将开发一种新方法，用于组装微小的金纳米颗粒簇，使其能够有效地进行光学读出，并安全地通过身体并靶向感兴趣的病变细胞。这些簇将被包裹在一个经过验证的生物相容性包装中，该包装增强了穿过生物屏障的运输，并被修改以使它们能够选择性地吸引到患病细胞。最重要的是，我们汇集了独特的能力：从许多厘米深的集群中非侵入性地读出多个信号;建立安全的集群，这些集群将随着时间的推移而自行解体。（例如小时）转化为可以从体内排出的更小的安全单位;调整这些结构的大小和内容物，使光能够通过加热或药物输送触发治疗反应;并在治疗过程中提供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最大限度地减少对健康组织的附带损害。此外，拟议的纳米治疗诊断方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。这利用功能化的金纳米颗粒从报告分子产生特定的光谱特征（通过表面增强的拉曼- Sers），所述报告分子用来自体外的低强度、安全的近红外激光照射。这为在体内实时识别和定位疾病的不同表达开辟了道路，同时靶向许多特定的分子靶标。近红外光在组织和细胞中几乎不被吸收，并且是非癌症的（与紫外线不同），从而促进安全，定期非侵入性监测治疗或疾病进展的可能性。在不久的将来，患者将有专门针对其需求选择的有效和有限的治疗，以最大限度地提高任何必要治疗的治疗价值，并防止任何不必要的，并且通过副作用和治疗可能有害。这不仅有可能提高生存率，而且有可能提高目前临床系统中可能提供主要治疗的患者的生活质量，每年还可能为英国各地的无效治疗节省1亿英镑。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重大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.