Taxol Bristle Ball

Cancer-clogging drugs loaded onto nanospheres from Rice University

Rice chemists have discovered a way to load dozens of molecules of the anticancer drug paclitaxel onto tiny gold spheres. The result is a 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.

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. 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."

The 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 drug - was not easy. Only a specific region of the drug binds with microtubules. This region of the drug fits neatly into the cell's support structure, like a chemical "key" fitting into a lock. Zubarev and 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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New Cancer Weapon

Nuclear Nanocapsules

Rice University chemists have found a way to package some of nature's most powerful radioactive particles inside DNA-sized tubes of pure carbon - a method they hope to use to target tiny tumors and even lone leukemia cells.


"There are no FDA-approved cancer therapies that employ alpha-particle radiation," said lead researcher Lon Wilson, professor of chemistry. "Approved therapies that use beta particles are not well-suited for treating cancer at the single-cell level because it takes thousands of beta particles to kill a lone cell.

By contrast, cancer cells can be destroyed with just one direct hit from an alpha particle on a cell nucleus."

In the study, Wilson, Rice graduate student Keith Hartman, University of Washington (UW) radiation oncologist Scott Wilbur and UW research scientist Donald Hamlin, developed and tested a process to load astatine atoms inside short sections of carbon nanotubes.

Because astatine is the rarest naturally occurring element on Earth - with less than a teaspoon estimated to exist in the Earth's crust at any given time - the research was conducted using astatine created in a UW cyclotron.

Astatine, like radium and uranium, emits alpha particles via radioactive decay. Alpha particles, which contain two protons and two neutrons, are the most massive particles emitted as radiation. About 4,000 times more massive than the electrons emitted by beta decay - the type of radiation most commonly used to treat cancer.

"It's something like the difference between a cannon shell and a BB," Wilson said. "The extra mass increases the amount of damage alpha particles can inflict on cancer cells."

The speed of radioactive particles is also an important factor in medical use. Beta particles travel very fast. This, combined with their small size, gives them significant penetrating power.

In cancer treatment, for example, beams of beta particles can be created outside the patient's body and directed at tumors. Alpha particles move much more slowly, and because they are also massive, they have very little penetrating power. They can be stopped by something as flimsy as tissue paper.

"The unique combination of low penetrating power and large particle mass make alpha particle ideal for targeting cancer at the single-cell level," Wilson said. "The difficulty in developing ways to use them to treat cancer has come in finding ways to deliver them quickly and directly to the cancer site."

In prior work, Wilson and colleagues developed techniques to attach antibodies to carbon fullerenes like nanotubes. Antibodies are proteins produced by white blood cells. Each antibody is designed to recognize and bind only with a specific antigen, and doctors have identified a host of cancer-specific antibodies that can be used to kill cancer cells.

In follow-up research, Wilson hopes to test the single-celled cancer targeting approach by attaching cancer-specific antibodies to astatine-loaded nanotubes.

One complicating factor in any astatine-based cancer therapy will be the element's short, 7.5-hour half-life. In radioactive decay, the term half-life refers to the time required for any quantity of a substance to decay by half its initial mass.

Due to astatine's brief half-life, any treatment must be delivered in a timely way, before the particles lose their potency.
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