Photodiagnosis and Phototherapy in Gastrointestinal Cancer: optimization using a novel microfluidics technology

School of Medicine

This project provides the opportunity to refine the technique of tissue-on-chip (ToC) microfluidic technology and to make it applicable for use in cancer therapy studies & treatment regimes. It will focus on the clinically relevant areas of photodiagnostic & photodynamic therapy (PD/PDT), in order to validate & provide proof of concept for this ToC platform technology. This project will be in collaboration with the School of Biomedical Sciences and the University of Hull. Salary for this project will be provided by LIBACS, with consumable funding from departmental resources. The aim of this project is to develop & use ToC simulation technology to evaluate PD/PDT as a diagnostic and treatment modality for human lower gastrointestinal cancers.

The development of more refined model systems will lead to a reduction & replacement of in vivo animal models in cancer research. ToC is one such technology that allows samples of human tissue to be kept alive for several weeks in a continuous microfluidics perfusion chamber (1). Addition of exogenous drugs to the perfusate enables the uptake and effect on the tissue to be studied in real-time. This technology, once optimized, can be used to test a range of drugs & delivery vehicles for cancer therapy and will facilitate the development of personalized cancer therapies. In this project, the initial focus will be on optimization of current PD/PDT drugs for the treatment of gastrointestinal cancers.

PD/PDT is ideally suited for application in gastrointestinal cancers. The abdominal cavity is readily accessible to light application, via a laparoscope, to activate a photosensitiser. The fluorescent light emitted by the photosensitiser can be used for in vivo photodiagnosis of cancers and metastases, and the secondary production of toxic oxidants can bring about cancer-specific cell death i.e. photosensitiser drugs have a unique theranostics capability. Despite the ease of application, there have been very few studies of PD/PDT in man, with proof of concept demonstrated only in small patient cohorts (2). The use of ToC technology in this project will enable us to study a range of photosensitisers to assess uptake, distribution, photodiagnosis, and photodynamic therapy in samples of human gastrointestinal cancer. Pharmacokinetic & pharmacodynamic (PK/PD) data will be correlated with therapeutic efficiencies by adjusting the excitation light intensity, allowing us to determine the therapeutic levels necessary for clinical translation. Novel strategies for cancer-specific delivery of photosensitisers (antibody mimetics and nanoparticles) to GI cancers will also be developed and tested using the ToC technology.

This project is an exciting opportunity to study novel strategies for anti-cancer therpy within a multidisciplinary team comprising molecular biologists, photochemists, and clinicians.

For informal enquiries regarding this project please contact Prof Jayne ([Email Address Removed])