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Sugar coating improves anticancer treatment

April 19, 2005 By Andreas von Bubnoff This article courtesy of Nature News.

Sweet nanoparticles successfully deliver drugs to mouse tumours.

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A coating of sugar could help nanoparticles deliver molecules to fight widespread tumours, according to research on mice.

The research team says its treatment could be adapted to a range of cancers and could move to clinical trials in two years' time. The results will be presented on 20 April at the annual meeting of the American Association for Cancer Research in Anaheim, California.

The team's nanoparticles, which contain gene-silencing molecules that can inhibit cancerous growth, are designed to be injected into the bloodstream and taken up primarily by tumour cells. This means the treatment should have fewer side-effects than, for example, chemotherapy, which affects all dividing cells in the body. The nanoparticles also manage not to create troublesome reactions from the immune system.

The study was conducted on mice with a form of cancer known as Ewing's sarcoma. There are currently few successful treatments for this cancer, but its growth can be stopped through the silencing of a single gene. "This was done as a model system, a proof of principle," says Timothy Triche of the Childrens Hospital Los Angeles, who led one of the two groups collaborating in the study.

Without treatment, eight out of eight study mice developed widespread cancer after three and a half weeks. But out of ten mice given twice-weekly injections of nanoparticles carrying a gene-silencing agent, only two showed cancerous growth, and this was relatively weak.

A spoonful of sugar

The nanoparticles, which are small enough to pass through blood vessels into the surrounding tissue, are taken up by cancerous cells because they carry a molecular tag that binds to receptors found on tumours. The agent consists of small interfering RNA (siRNA). When the agent is taken up by a tumor cell, it inhibits expression of the tumour-growth gene, and the cell stops multiplying.

Other attempts to carry siRNA to tumours have used nanoparticles made of lipids. But in some mouse studies, these particles provoked an immune response, which would make the approach difficult to use in humans.

To get around this problem, Mark Davis's group at the California Institute of Technology developed a polymer from a sugar-based molecule called cyclodextrin to encapsulate siRNA. Particles of this polymer spark no immune response, confirms team member Siwen Hu, also of the Childrens Hospital Los Angeles.

The team isn't sure why this is, and suggests that it may simply be because cyclodextrin nanoparticles are not taken up by immune cells.

"That's an intriguing possibility," says Ian MacLachlan of Protiva Biotherapeutics in Burnaby, Canada, who led one of the recent studies using lipids. He cautions that more research is needed to prove the utility of the sugar-based nanoparticles.

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