Development of pro-drugs and technology for light mediated treatment of Bladder Cancer

Non-muscle invasive bladder cancer constitutes 75% of all bladder cancer cases. It has very high recurrence rates of 60-70% with a progression rate of 20-30%. Only three drugs have been approved in the last 30+ years for this entity: Bacillus Calmette–Guérin (BCG), Thiotepa, and Valrubicin. To date, there are no standard therapies for patients after BCG failure, other than radical cystectomy.

There have been several photodynamic therapy (PDT) trials demonstrating promising results in bladder cancer patients, ranging from an early response rate of 45% to 90.9%. Photodynamic agents are non-toxic, but when exposed to light generate reactive oxygen species (ROS), which kill cells. Thus, local irradiation specifically kills the tumour leaving non-irradiated healthy cells unharmed, reducing toxic side-effects. To date all approved PDT agents are organic molecules, but the photophysical properties of many transition metal complexes make them ideal PDT candidates. Their key advantage over organic molecules is the heavy atom effect, which favours fast singlet to triplet intersystem crossing (ISC). The longer lifetimes which result from ISC lead to high yields of 1O2 and/or other ROS. The ease of chemical modification, increased bioavailability and their photostability adds to the appeal of these complexes. We have synthesized a series of related Ir(III) containing complexes that in preliminary studies have been shown to have PS activities.

We now seek a motivated PhD student to translate the preliminary findings into a range of bladder cancer models. You will analyze chemistry properties, PDT activity, cellular localization and mechanism of action. This work is a collaboration with the Rutherford Appleton Laboratory operated by the Science and Technology Facilities Council, UK and our industrial partners K-laser, UK.

This highly interdisciplinary and translational project will give training in a wide range of techniques, cell biology, confocal microscopy, complex in vitro disease models, laser spectroscopy, emission imaging, basic synthetic chemistry, and will put the student in a prime position with regard to career prospects.

More details on each lab and collaborators can be found:

https://www.sheffield.ac.uk/medicine/people/oncology-metabolism/helen-e-bryant

https://www.sheffield.ac.uk/chemistry/people/academic/julia-weinstein

https://stfc.ukri.org/about-us/where-we-work/rutherford-appleton-laboratory/

https://klaseruk.co.uk/

Entry Requirements:

Candidates must have a first or upper second class honors degree or significant research experience. Experience of chemistry or at least biochemistry would be preferable.

How to apply:

Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select 'Oncology & Metabolism' as the department. 

Enquiries:

Interested candidates should in the first instance contact Dr Helen Bryant - h.bryant@sheffield.ac.uk