A coating of sugar could help nanoparticles deliver molecules to
fight widespread tumours, according to research on mice.
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,
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
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
John Martin is a long-time health
journalist and an editor for Priority Healthcare. His credits
include overseeing health news coverage for the website of Fox
Television's The Health Network, and articles for the New York
Post and other consumer and trade publications.