Title: Nanoscale electrochemistry of brain cancer cells
Funder: The Academy of Medical Sciences

Abstract: Glioblastoma (GBM) is the most common form of glioma in adults and among the most devastating cancer. GBM biology remains poorly understood with an unmet clinical need for the development of alternative therapeutic strategies. GBM frequently recurs from residual tumour cells surviving chemotherapy which often linked to redox flux and mitochondria metabolism. These complex processes involve spatially heterogeneous interactions of brain cancer cells, which have been proved difficult to probe with existing techniques. Thus, the study of brain cancer cell biology and the mechanism of different spatial heterogeneous redox processes is of high importance in biomedical science. Nanotechnology, based on the use of scanning electrochemical microscopy-scanning ion conductance microscopy (SECM-SICM), has a fundamental impact to revolutionise cancer diagnosis and therapy. I aim to exploit biological activities of brain cancer cells using high-resolution microscopy technique (SECM-SICM) coupled with redox molecules. My vision is that the advanced nanoscale imaging technique with excellent spatial resolution will offer entirely new views of the heterogeneous processes on cancer cells at the nanoscale. The nanoscale platform will advance the cancer diagnostics and therapies, and provide insights beyond those attainable from microscopic techniques. The research will focus on addressing key questions: (1)what is causing the heterogeneous electron transfer process and understand the transport of redox mediator through ion channel membrane? (2)what is the electron transfer mechanism of a ferrocene-based redox mediator in the cell and the characterisation the secreted redox mediator produced from the cell? (3)what are the tumour-promoting mechanisms and their relationship with cancer treatment strategies?

Lay abstract: Glioblastoma is the most lethal brain cancer, and the five-year survival is <​5%. Globally, the brain tumour drugs market is extremely important (£2 Billion annually, Fortune Business Insights). Our vision is that the multifunctional nanoscale electrochemical imaging platform will cause a step change for the investigation of physicochemical processes of brain tumour cells. The platform will provide insight for the understanding of brain tumour biology and its connection to drug development. My proposed programme will help to strengthen the UK’s position as a world leader in this research area of high economic impact. The development of a new platform capable of brain cancer cell biology and the tumour promoting mechanism investigation in this proposal, is extremely timely. A huge challenge in modern healthcare lies particularly in finding more effective ways to treat brain cancer patients. Limited progress on the understanding of the biological and heterogeneous characteristics of the cancer cells poses enormous challenges for cancers treatments. This project will illuminate the development of new strategies based on the understanding of fundamental biology for brain cancer cells and their relationship with cancer therapies. The project will focus on the development of a novel and promising approach and carry out experiments at a single cell level. The main scientific outcomes are: 1)the development of a nano-imaging platform; 2)improving the understanding of the brain cancer cell biological processes; 3)the development of a computational/experimental protocol for the investigation of cancer treatment performance. These findings will be critical to efficiently prevent/detect diseases and improve/design therapies.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS