Taxol bristle ball: a wrench in the works for cancer

Sep 12, 2007
TaxolBall
Using gold nanoparticles, Rice chemists have created tiny spheres that literally bristle with molecules of the anti-cancer drug Taxol. Credit: Eugene Zubarev/Rice University

Rice University chemists have discovered a way to load dozens of molecules of the anti-cancer drug paclitaxel onto tiny gold spheres. The result is a tiny ball, many times smaller than a living cell that literally bristles with the drug.

Paclitaxel, which is sold under the brand name Taxol®, prevents cancer cells from dividing by jamming their inner works.

"Paclitaxel is one of the most effective anti-cancer drugs, and many researchers are exploring how to deliver much more of the drug directly to cancer cells," said lead researcher Eugene Zubarev, the Norman Hackerman-Welch Young Investigator and assistant professor of chemistry at Rice. "We looked for an approach that would clear the major hurdles people have encountered -- solubility, drug efficacy, bioavailability and uniform dispersion -- and our initial results look very promising."

The research is available online and will appear in the Sept. 19 issue of the Journal of the American Chemical Society.

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."

Citation: J. Am. Chem. Soc. 2007, vol. 129, pgs.11653-11661

Source: Rice University

Explore further: Na-ion batteries get closer to replacing Li-ion batteries

add to favorites email to friend print save as pdf

Related Stories

New strategy to combat 'undruggable' cancer molecule

Jan 26, 2015

Three of the four most fatal cancers are caused by a protein known as Ras; either because it mutates or simply because it ends up in the wrong place at the wrong time. Ras has proven an elusive target for ...

Origami—mathematics in creasing

Jan 07, 2015

Origami is the ancient Japanese art of paper folding. One uncut square of paper can, in the hands of an origami artist, be folded into a bird, a frog, a sailboat, or a Japanese samurai helmet beetle. Origami can be extraordinarily complicat ...

A key component of cell division comes to light

Jun 30, 2014

The division of a cell in two requires the assembly of the mitotic spindle, an extremely complex structure, which is the result of the coordinated action of a multitude of proteins and a finely tuned balance ...

Recommended for you

What causes the sunlight flavour in milk?

4 hours ago

Most of us have tasted milk that has been left in the sun – it has a distinctive off-flavour. The reason is that milk and other dairy products turn rancid when exposed to light.

Scientists find clues to cancer drug failure

22 hours ago

Cancer patients fear the possibility that one day their cells might start rendering many different chemotherapy regimens ineffective. This phenomenon, called multidrug resistance, leads to tumors that defy ...

Smart crystallization

Mar 02, 2015

A novel nucleating agent that builds on the concept of molecularly imprinted polymers (MIPs) could allow crystallographers access to proteins and other biological macromolecules that are usually reluctant ...

Supersonic electrons could produce future solar fuel

Mar 02, 2015

Researchers from institutions including Lund University have taken a step closer to producing solar fuel using artificial photosynthesis. In a new study, they have successfully tracked the electrons' rapid transit through ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.