Next-generation long-acting therapeutics for malignant brain tumours

'Glioblastoma', the most common malignant brain cancer, remains incurable despite multimodal standard-of-care treatment (surgery, followed by adjuvant radiotherapy and chemotherapy). In considerable part, this is due to otherwise potent chemotherapy drugs failing to cross the blood-brain-barrier effectively, and lack of targeting these drugs specifically to glioblastoma cells in the brain, thus sparing healthy brain cells.

The aim of this research project is to synthesise and characterise biomaterial-based delivery systems which enable long-acting therapeutic release, with the objective of a single dose administration resulting in an efficacious outcome.

Initial experiments will be conducted using patient-derived glioblastoma cell lines to identify those likely to be sensitive to this mode of therapy. Methodologies will include hydrogel and nanoparticle formulation/characterisation, 2D and 3D tumour organoid cultures (cytotoxicity assays), and confocal microscopy (intracellular drug uptake and accumulation).

The final series of experiments will test the potential efficacy of lead formulations using patient-derived xenograft mouse models of glioblastoma. A key outcome measure will be overall survival relative to animals treated with glioblastoma standard -of-care. This will generate proof-of-concept data to expedite a route to clinical translation.