A technique for studying anticancer drugs inside cells could help in the search for better-targeted cancer therapies.

Trevor Hambley and co-workers from the University of Sydney, Australia, have used their new coordination-sensitive fluorescence technique to monitor platinum drugs of different coordination state - Pt(II) and Pt(IV) - inside cells. Their aim is to track the differences in how the complexes are handled by cells.

'Platinum drugs work by binding to DNA but they do so in healthy cells as well as tumour cells, causing toxicity,' explains Hambley. So whilst Pt(II) complexes such as cisplatin are active against cancer, their toxicity to healthy cells can also lead to side effects. The advantage of Pt(IV) complexes is that they are much less reactive than Pt(II), but they reduce to form the highly active Pt(II) species. If Pt(IV) drugs could be reduced to Pt(II) only once they are inside a tumour, they should be effective against cancer while having low toxicity.

But, as Ulrich Bierbach, who researches platinum anticancer drugs at Wake Forest University, North Carolina, US, explains, little is known about how these drugs act in the cell, despite many years of intense research. Approaches such as Hambley's help to trace the pathways these complexes take inside cancer cells so the method 'will ultimately help improve the pharmacological properties of current and future platinum-based therapies,' says Bierbach.

Hambley's group made Pt(II) and Pt(IV) complexes containing a fluorescent ligand and treated cancer cells with them. By using confocal fluorescence microscopy to study the fluorescence in the cells, the researchers found that the Pt(II) complexes showed higher fluorescence than Pt(IV), and when Pt(IV) is reduced to Pt(II), there is an increase in fluorescence. 'We used differences between the images to gather information on how the compounds are handled by the cells,' explains Hambley. 

Hambley says that he hopes to track where in the cell Pt(IV) complexes are reduced to Pt(II), by monitoring fluorescence changes over time. The group is also working on strategies for restricting Pt(IV) complex reduction to the tumour environment.

Fay Riordan

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