Intratumoral monitoring of hypoxia in vivo in real time using nanosensor technology

Lead Research Organisation: University of Nottingham
Department Name: Nottingham Digestive Diseases Centre

Abstract

This project will provide a senior scientist working in a Cancer laboratory with training in a physical sciences technology which may be applied to the development of cancer treatments. During rapid tumour growth, some areas of cancers do not receive an adequate supply of oxygen and other nutrients. This turns on cellular pathways which enhance cell survival and increase the resistance of the cells to standard treatments for cancer such as radiation and chemotherapy. Therefore, a sensitive method for monitoring oxygen levels within tumours on an ongoing basis is required. One possible approach is to use small particles containing fluorescent dyes (nanosensors), which change colour when the oxygen concentration changes. Such particles could be used to monitor oxygen concentrations within tumours and, ultimately, to trigger treatments under defined conditions. Fluorescent nanosensors have already been developed and this project will investigate the possibility of applying them to monitoring oxygen concentrations in whole tumours. In addition, more sensitive light emitting nanosensors will be developed.

Technical Summary

This project will enable a Chief Experimental Officer working within a Life Sciences setting (Academic Unit of Cancer Studies, AUCS) to receive training in the design, synthesis and analysis of nanosensor technology within a Physical Sciences laboratory (Laboratory of Biophysics and Surface Analysis, LBSA) and to apply these skills to an important clinically-relevant problem of in vivo hypoxia monitoring. Temporal changes in blood flow and oxygenation result in subtle alterations in tumour-associated hypoxia on an ongoing basis, affecting treatment efficacy. Nanosensor technology provides a potential solution to this problem. The programme of work aims to apply fluorescent nanosensor technology to monitor oxygen levels, metabolic activity and acidity during tumour formation in vivo in real time in relation to blood vessel formation and to develop bioluminescent nanosensors which will provide a higher degree of sensitivity. The project will broaden the Chief Experimental Officer?s skills base, and facilitate future interactions between AUCS and LBSA, as well as between AUCS and other scientists from a physical sciences background with technology applicable to understanding tumour biology or cancer therapy. It will also allow LBSA to refine its technology and expand its applications.

Publications

10 25 50