Design and Development of Functional Nanoparticles as Contrast Agents for Magnetic Resonance Imaging (MRI).

Aims: To design and develop nanomaterials as multifunctional targeted therapeutic and diagnostic agents. This includes the production of contrast agents with enhanced MR imaging capabilities than reported analogues, stimuli-responsive agents and investigation of new platforms for enhancing MR contrast. In addition, the underlying mechanism of proton relaxation will be investigated for mesoporous silica manoparticles (MSNs) doped with Dy3+.Description and Potential Impact: Nanotechnology is defined as the study of materials with at least one dimension in the nanometre range (1-100 nm). Due to nanometric sizes, nanomaterials have the ability to offer improved physical, chemical or biological properties, with a wide ranging chemical tunability and higher surface area-to-volume ratio over molecular analogues allowing for greater manipulation of matter. One application of nanotechnology is the use of nanomaterials as contrast agents for MRI. Enriched diagnostic capabilities can be achieved via the use of stimuli-responsive particles where water access to the MR active paramagnetic chelate is reversibly gated, switching the contrast capabilities on/off. This allows for a significant change in the contrast differential within a particular pathological region.Within this project a novel micellular platform will be investigated. By investigating different monomers, chain transfer agents, and different chain lengths the contrast capabilities can be compared. The scope to alter this platform is endless, with the ability to introduce stimuli-responsivity vital for disease specific diagnosis e.g. pH-responsive agents for cancerous tissue. In addition to his work, MSNs doped with paramagnetic Dy3+ will also be studied. By tuning the loading density of Dy3+ and optimising the generated T2 contrast the Curie dependence on relaxivity can be further explored. The production of a MRI contrast agent with improved biocompatibility, a contrast switch 'on' within a disease-specific microenvironment and greater performance than current clinical analogues would be an invaluable asset in the way disease progression and response to treatment is monitored. These aims form the main focus of this project, with the hope that the methods and results will be truly impactful in MRI diagnostics. Novelty of the Research Methodology: The design, development and characterisation of new MRI probes with enhanced contrast capabilities, including stimuli-responsive properties. Further understanding of the theory behind contrast enhancement and the controlling factors. Alignment to EPSRC's Strategies and Research Areas: Several EPSRC research areas are encompassed in this project. The production of MRI active nanomaterial systems as potential contrast agents providing non-invasive and improved diagnosis falls under the remit of Healthcare Technologies. In addition, the project covers Manufacturing for the Future since stimuli-responsive systems are applicable for an enhanced diagnosis of a plethora of diseases, e.g. deviations in pH are present within cancerous tissue. Finally, the project falls within the EPSRC Physical Sciences research area since the theory and methods stem from several branches of Chemistry.