In Situ Nanoparticle Assemblies for Healthcare Diagnostics and Therapy

There is a growing need for clinicians to be able to diagnose and prescribe therapy according to an individual's healthcare needs and potential responses. To allow this personalised medicine approach to be fulfilled, new technologies allowing rapid and accurate detection of biomarkers indicative of specific diseases are needed and to be available to clinicians to aid in their management of disease. This proposal aims to bring together physical scientists working on nanoparticles capable of detecting biomarkers at ultralow concentrations with information technologists capable of interpreting and presenting data from these complex assays to the clinical partners who are interested in how best to utilise this new information in improved healthcare practice. The basis of the proposal is to create an in vitro diagnostic assay at first which is capable of detecting multiple biomarkers in a patient's sample which allows the clinician to produce a risk profile of the patient. A second aspect of the research is to investigate in vivo imaging by SERS for specific biomarkers and in a multiplexed manner. The disease we are targeting is cardiovascular disease which covers atherosclerotic plaques. Risk of atherosclerosis is identified by increased levels of specific biomarkers, however, atherosclerosis is characterised by a localised rather than a systemic immune response. Therefore the measurement of biomarkers for in vitro prediction will be investigated in parallel to quantification of vascular inflammation and the development of a therapeutic approach to convey treatments directly to the affected vessel. The assays will be based on surface enhanced Raman scattering (SERS) and use metallic nanoparticles. The output will be in the form of a vibrational spectrum which will contain a high degree of information relating to the relative quantitation of each of the specific biomarkers being investigated. Two types of in vitro assay will be investigated with one of them carrying forward for in vivo imaging. The in vivo assay will recognise the target and through interpretation of the signal allow a decision to be made whether to induce a therapeutic action. The action we are proposing is a photothermal response from an assembly of the nanoparticles triggered by the specific biomarker being interrogated. This makes the response highly specific to that biomarker and will offer a new way to manage atherosclerosis.

There are a number of different communities who will benefit from the research outputs and improved capacity from this research and again this grouping of communities will be included in our User Engagement Strategy. The most immediate beneficiaries will be the general public who will ultimately be exposed to improved capability in terms of healthcare diagnostics and management. We are proposing to integrate physical sciences, data interpretation and clinical utilisation. The end result from this will be an improved opportunity for clinicians to manage the disease types we are concentrating on and in turn pass on these benefits and improved capability to the patients. This will result in shortened hospital time with more appropriate administration and prescription of therapeutic drugs which in turn minimises potential side effects to the patient and also improves the economics of healthcare by reducing the amount of drugs necessary for prescription. That is of course assuming that the prognosis from the analysis is that minimal drug intervention can be employed. We also see this as a significant benefit in terms of quality of life and in terms of health and wellbeing for the general public. The clinical partners are influential in terms of medical research and medical policy making. e.g McInnes is chair of the newly created Arthritis Research UK New Agents Committee, leader of the CSO/Pfizer co funded Scottish Early Arthritis Research Programme and has strong links with the pharmaceutical industry serving as chair or participant in a range of Industry drug development programmes at the global level. These examples provide evidence of the potential for significant impact. In addition to specific healthcare outcomes we also see opportunities for engagement with a range of industry partners who will be interested in different aspects of the impact from this research. This will include manufacturers who are capable of producing systems necessary for the combined measurements we are proposing (project partner), reagent suppliers who are interested in the specific chemistries employed, software developers who are looking to implement new software approaches to medical problems and also to the pharmaceutical companies who are interested in more efficient prescription of their medicines. We see impact in all of these sectors and will look to engage with these different areas of exploitation as we implement our Impact strategy. Three of the investigators have direct experience of spin-out which is a benefit to both the project and also the end user community. We are uncertain whether there are spin-out opportunities directly arising from any of the intellectual property which will be created during the project however this is something which we will regularly review and use our experience to inform our decision making process on as we progress.