Dendrimers offer new cancer treatment route

The toxicity of cancer drugs has been a problem since they were first developed, and researchers are constantly looking for new ways to ensure that they kill only cancer cells, rather than healthy cells elsewhere in the body.

The latest attempt at designing a cancer-specific smart delivery system, from the University of Michigan in Ann Arbor, focuses on dendrimers, multiply-branched molecules whose name derives from their resemblance to trees.

Dendrimers drew the attention of the team, led by Professor James Baker of the U-M Centre for Biologic Nanotechnology, because of their structure they are nanosized spheres consisting of thousands of individual hydrocarbon chains. The free ends of these chains are potential attachment points for other molecules.

'For example, you could attach a targeting agent that can distinguish it from a healthy cell. You can also attach the drug which actually kills the cancer cells,' explained team member Almut Mecke. 'If you have both of these functions on the same molecule, then you have a smart drug that knows which cells to attack.'

There is, of course, a problem dendrimers are themselves toxic, capable of entering cells and killing them. Using an atomic force microscope, Mecke studied the reaction between the molecules and cells, and found that the dendrimers appear to punch directly through cell walls. 'Dendrimers have a charge, and so do cell membranes,' she says. 'It's the interactions between these charges that cause the dendrimers to bind to cell membranes and disrupt them.'

This is not a desirable property for a cancer drug, but the team has found that the surface charge can be neutralised, which renders the dendrimers safe. These uncharged dendrimers can then be modified with the targeting groups and despite their lack of charge, they will still bind to and enter cancer cells 'and only cancer cells and that's what we want,' Mecke says.

The team has already carried out some small-scale trials with mice using dendrimers modified with chemotherapy agents and targeting cells. The drugs remained active and caused fewer side effects than conventional therapy, Mecke says. The next stage of the research will see the team attaching additional groups to the dendrimers, such as biosensors that can show whether an attacked cell has been killed.