ProfessorTrevor Hambley

Project Opportunities

Title: Targeted delivery of anticancer agents

Summary of opportunity:

An ideal anticancer agent is one that is inert as it moves around the body, is selectively taken up by cancer cells, and is activated once inside those cells. The multiple oxidation states with different reactivities available to metals such as platinum and cobalt provide a means of turning off activity and cells are able to turn it back on. The challenge is to find targeting mechanisms that deliver sufficient of these agents to kill the cancer cells and this is the focus of our work.

Opportunity synopsis:

Platinum(IV) Based Anti-Cancer Drugs 
Pt(IV) complexes are reduced in cells to Pt(II) and then are believed act in the same way as agents such as cisplatin. Our goal is to develop Pt(IV) complexes that survive in the blood stream and are selectively taken up by cancer cells. The aim of the present projects is to investigate one of a number of methods for the selective uptake of the Pt(IV) anti-cancer compounds by tumour cells and then to investigate the behaviour of the targeted complexes in cancer cells and in models of solid tumours. 
Cobalt Complexes as Chaperones of Anti-Cancer Agents 
Almost all drugs used in the treatment of cancer cause serious side effects because they lack selectivity for tumours. Coordination of some anticancer agents to Co(III) makes them inactive, but uptake of the complex by cells results in release and reactivation of the anticancer agent. If the complexes can be targeted to cancer cells, the cobalt can effectively chaperone the anticancer agent to where it is needed. Thus, the goal of our work is to develop new agents that selectively target solid tumours by taking advantage of the differences between the tumours and healthy tissues. The aims of this project are to develop new cobalt-based complexes which are either hypoxia-selective or are tagged with a group taken up more rapidly by cancer cells. In order establish the effectiveness of the approach we will use complexes with fluorescent tags to monitor uptake, distribution and reactivity in caner cells and tumour models.