MRC DiMeN Doctoral Training Partnership: A novel theragnostic approach for treating brain tumours

This multidisciplinary project will use cutting edge imaging technologies along with novel chemistry and a cell-based therapy to treat glioblastomas, the deadliest form of brain cancer in adults. These tumours have a dismal survival of less than 14 months. Despite aggressive treatment, tumours usually recur within 6-9 months, hence there is a dire need for developing novel ways of treating glioblastomas. Magnetic Fluid Hyperthermia (MFH) is novel way for targeted tumour ablation (heating) as it specifically heats nanoparticles in the tumour without any adverse effects to the normal tissue.

The overall aim of this project is to develop a novel treatment paradigm for glioblastomas using the following goals: 1) Development of xenograft models of glioblastomas and their characterization using longitudinal high-resolution MRI. 2) Developing targeted delivery of custom designed super-paramagnetic iron oxide particles (SPIONs) to the tumour using endothelial progenitor cells (EPCs) labelled with SPIONs. 3) Assessment of preferential localization of SPIONs in the tumour using magnetic particle imaging (MPI) scanner. 4) Developing selective heating of the SPIONS in the tumour using MFH to ablate the tumor without impacting the normal tissue. 5) Monitoring MFH induced treatment response using advanced MRI methods.

Novelty: This project aims to develop a novel therapeutic strategy for treatment of glioblastomas without any adverse effects to the surrounding normal tissue. It uses novel imaging technologies – magnetic particle imaging, and MFH for hyperthermia, which are the first of its kind in UK and Europe.

Training: The primary supervisor, Prof Harish Poptani (https://www.liverpool.ac.uk/people/harish-poptani#tabbed-content) has expertise in quantitative imaging methods for assessing treatment response in glioblastomas. He will provide training in the development of preclinical models, multi-modal preclinical imaging techniques as well as optimization of MFH for treatment. The secondary supervisor, Dr Marco Giardiello (https://www.liverpool.ac.uk/people/marco-giardiello) is a senior lecturer and a UKRI future leaders fellow His expertise is in synthetic chemistry focussing on development of novel custom built fit-for-purpose contrast agents for MRI and MPI. In collaboration with StreamBio (https://www.streambio.co.uk/) the industrial partners in this project, he will provide training in the synthesis of SPIONs towards optimal sensitivity for detection with MPI and treatment with MFH. The tertiary supervisor, Prof Patricia Murray (https://www.liverpool.ac.uk/people/patricia-murray) is internationally known for her expertise in stem cell biology and will provide training in cell biology, cell labelling methods as well as immunohistochemical analyses.  In addition, the student will spend a minimum of three months training with our industrial partner, during which the student will be trained in the manufacture of StreamBio particles and undertake QA analysis. The student will also be exposed to the development of a commercialization and marketing strategy for new particles generated during the project.

This collaborative project brings together complementary expertise in neuro-oncology, neuroimaging, synthetic chemistry and stem cell biology. Besides training in highly sought after skills, additional real life work experience in the synthesis of nanoparticles will be provided by our industrial collaborator. The collective backgrounds of the supervisors provide complementary expertise in tackling the complex interplay between, tumour microenvironment and novel medical technologies for diagnosis and treatment of tumours. 

iCASE industrial partner web link: https://www.streambio.co.uk/

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of-the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, training opportunities or internships in science policy, science communication and beyond. Further information on the programme and how to apply can be found on our website:

https://www.dimen.org.uk/