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Using gold nanoparticles, Rice
chemists have created tiny spheres that literally bristle with
molecules of the anti-cancer drug Taxol.
Image by Eugene Zubarev/Rice
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The research is available online
(see below) and will appear in the Sept. 19
issue of the Journal of the American Chemical Society (J. Am. Chem.
Soc. 2007, vol. 129, pgs.11653-11661).
First isolated from the bark of the yew tree in 1967, paclitaxel is
one of the most widely prescribed chemotherapy drugs in use today. The
drug is used to treat breast, ovarian and other cancers.
Paclitaxel works by attaching itself to structural supports called
microtubules, which form the framework inside living cells. In order
to divide, cells must break down their internal framework, and
paclitaxel stops this process by locking the support into place.
Since cancer cells divide more rapidly than healthy cells, paclitaxel
is very effective at slowing the growth of tumors in some patients.
However, one problem with using paclitaxel as a general inhibitor of
cell division is that it works on all cells, including healthy cells
that tend to divide rapidly. This is why patients undergoing
chemotherapy sometimes suffer side effects like hair loss and
suppressed immune function.
"Ideally, we'd like to deliver more of the drug directly to the cancer
cells and reduce the side effects of chemotherapy," Zubarev said. "In
addition, we'd like to improve the effectiveness of the drug, perhaps
by increasing its ability to stay bound to microtubules within the
cell."
Zubarev's new delivery system centers on a tiny ball of gold that's
barely wider than a strand of DNA. Finding a chemical process to
attach a uniform number of paclitaxel molecules to the ball - without
chemically altering the drugs -- was not easy. Only a specific region
of the drug binds with microtubules. This region of the drugs fits
neatly into the cell's support structure, like a chemical "key"
fitting into a lock. Zubarev and graduate student Jacob Gibson knew
they had to find a way to make sure the drug's key was located on the
face of each bristle.
Zubarev and Gibson first designed a chemical "wrapper" to shroud the
key, protecting it from the chemical reactions they needed to perform
to create the ball. Using the wrapped version of the drug, they
undertook a series of reactions to attach the drug to linker molecules
that were, in turn, attached to the ball. In the final step of the
reaction, they dissolved the wrapper, restoring the key.
"We are already working on follow-up studies to determine the potency
of the paclitaxel-loaded nanoparticles," Zubarev said. "Since each
ball is loaded with a uniform number of drug molecules, we expect it
will be relatively easy to compare the effectiveness of the
nanoparticles with the effectiveness of generally administered
paclitaxel."
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