Collaborations: Prof. Dr. Nils Metzler-Nolte of Ruhr-Universität, Bochum, Germany
There is an urgent need to develop selective treatments for cancer. Current treatments are not selective enough and cause debilitating and toxic side effects therefore compromising the effectiveness of the treatment.
It is important to develop more tumour selective drugs which are taken up more uniformly and/or selectively activated in the tumour environment, particuarly in the hypoxic regions of solid tumours. For instance, the diffusion of doxorubicin in tumours has recently been shown to fall off exponentially with a half-distance of as little as 40 Ám. The goal of this project is to develop more tumour selective anticancer agents based on a knowledge of their uptake, three dimensional distribution, and fate.
Radiolabelling of drugs provides information on distribution, but only at a limited resolution and tagging of analogues with fluorophores provides much useful information, but potentially modifies the uptake and distribution. Our research group employs new approaches such as X-ray and fluorescence spectroscopy and microscopy to monitor the disposition of metal-based anticancer drugs in tumours.
Confocal images of A2780 cells showing uptake of fluorescent tagged Pt(II)
Platinum complexes are arguably the most widely used anticancer agents in the world and are included in the treatment regimes in more than half of all cancer patients. The uptake, distribution and fate of a range of the more reactive platinum(II) and the more inert platinum(IV) complexes are being investigated in this project. Cobalt(III) complexes are also being investigated as potential hypoxia-activated prodrugs.