Investigating the cellular interactions and uptake of therapeutic nanoparticles in the treatment of brain cancer
Primary supervisor: Professor Corinne Smith, School of Life Sciences
Non-academic partner: Xerion Healthcare Ltd
Project Title: Investigating the cellular interactions and uptake of therapeutic nanoparticles in the treatment of brain cancer
Oxilia nanoparticles represent a powerful tool in the treatment of cancer by enhancing the effects of radiotherapy in destroying tumour tissue. They show particular promise as a therapeutic agent due to their ability to act on hypoxic tumours, which are otherwise resistant to radiotherapy, and are currently being developed for use in head and neck cancers.
In this collaboration between Xerion Healthcare and Dr Corinne Smith, University of Warwick, we seek to broaden the applicability of these nanoparticles to use in brain cancer. High grade brain tumours have an extremely bleak prognosis, with most studies showing very little or zero 5 year survival. Median time from diagnosis to death is 14.6months with current best supported care. This has increased by only 3.3 months over the last 25 years due to near universal reoccurrence following resection, radiotherapy and chemotherapy. Treatment of the tumour bed following resection is key to improving survival. The ability of these nanoparticles to enhance the effects of post-surgical radiotherapy, creates an opportunity to tackle local recurrence of tumours through their application to the tumour bed at the point of surgery.
However, in order to be able to apply use of these nanoparticles for brain tumour treatment, their behaviour in the different cellular context of the brain needs to be characterised. This requires study of the interaction of nanoparticle formulations with healthy and tumour-causing brain cells, and investigation of the cellular processes that mediate their uptake using electron microscopy and live cell imaging.
The project aims to address the questions:
- What determines absorption of therapeutic nanoparticles into brain tumour (U87 glioblastoma) cells or healthy astrocytes?
- How do the components of the formulation dictate the entry and progress of nanoparticles into tumour tissue?
During the project the student will use nanotechnology, cell biology and both light and electron microscopy imaging to address these questions via the following experimental aims.
- Interaction of nanoparticles with healthy normal astrocytes and glioblastoma cells in 2D cell culture
- Analysis of nanoparticle distribution in neuronal cells and mouse tumours
- Characterisation of nanoparticle uptake and distribution in 3D cultures
By establishing the mode of interaction of Oxilia nanoparticles in the context of brain tumour cells this project will determine the feasibility of transfer of this important therapeutic approach to treatment of some of the most serious types of cancer.
Contact: Professor Corinne Smith, University of Warwick