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

Lead Research Organisation: University of Exeter
Department Name: Physics

Abstract

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.

Planned Impact

The major impact from this PG will be to establish a platform healthcare technology, in a significant area of increasing clinical need, to provide stratified diagnosis and therapy in a single modality. It will have the significant potential to improve patient outcomes (lower mortality/less aggressive treatments); reduce dramatically the financial burden of healthcare and provide a catalyst for UK novel healthcare technology industries. This will be achieved by developing industry and healthcare partnerships to develop solutions for specific disease targets that will be first tested in pre-clinical studies and lead to full in vivo clinical trials.

Here we propose to develop an advanced diagnostic platform addressing the critical clinical needs of the next generation of healthcare, combining non-invasive in-vivo detection and diagnosis of disease with targeted, light-mediated therapeutics and real-time treatment monitoring. The initial targets of this novel approach will be subsurface cancers and their associated metastases; such as breast, prostate, head and neck cancers and associated metastases (secondary cancers). This will be achieved by bringing together several unique technologies, established by the applicants in their respective fields, who have already evidence of collaborating. These when integrated will yield exceptionally high added value providing the capability of delivering Raman Nanotheranostics in a safe, effective and minimally invasive (non-surgical) manner.

We will make use of the EPSRC translation toolkit, benefitting patients and UK academia. A major impact on the UK economy will also be accrued. (Cancer diagnosis and therapy is expected to cost >£15B by 2021.) The new platform technology may also be applicable elsewhere - eg in glucose detection, infectious diseases, Alzheimer's and other degenerative diseases.

This is a highly challenging programme with high level risks balanced by exceptionally high benefits to the society if delivered a proposed. The risks are mitigated by bringing together world-leading experts to deliver each of our pillar technologies, through carefully coordinated sub-programmes, followed by careful integration. Each element of this programme will facilitate breakthroughs, stimulating the nascent field in numerous ways with extra added value stemming from their integration into a unique diagnostic-therapy.

The programme partners will establish a Clinical Collaborator Group to provide insight to key clinical needs and an International Advisory Board to provide advice on identifying and translating new clinical technologies into commercial products for the benefit of patients. One of the major outputs of this programme will be to ensure we develop realistic future healthcare technologies, by use of our IAB, public engagement events - discussing patient's views on use of nano-technologies, outlining their potential - and careful health economic evaluation (cost/benefit analysis) of the technologies versus specific clinical needs.

The PI and CIs have experience of translating technologies from bench to bedside and are aware of the need to de-risk the concepts and technologies we develop to ensure industrial support is forthcoming to drive it to the market in a timely manner.

Ultimately patients will benefit from better clinical decisions being taken, with enhanced knowledge provided by the direct measure of the tissue composition and associated physiology. The health service will benefit by having to provide less secondary procedures and clinics in addition to potentially reducing the need for radical cancer treatments in those with early lesions. The commercial sector and UK plc will benefit from the implementation of such methods (and associated spin offs).
 
Title Data for Metasurfaces atop Metamaterials: Surface Morphology Induces Linear Dichroism in Gyroid Optical Metamaterials 
Description Data from all the figures in this paper. Please see the README file (Dataset.pdf) for descriptions of each subfolder. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Description Press release outlining the plans for the RaNT Programme 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Each partner provided press releases for inclusion in wider media across the UK.
Year(s) Of Engagement Activity 2018
URL https://www.exeter.ac.uk/news/featurednews/title_635440_en.html