Nanotherapy: gold-drug combo could target tumors.

Looking for a way to deliver a chemotherapy drug to cancer patients more safely and effectively, a team of chemists has attached dozens of paelitaxel (Taxol) molecules to tiny gold particles that could carry the drug directly to a tumor in the body.

Paclitaxel, first isolated from the bark of the Pacific yew tree in 1967, is widely prescribed for people with lung, ovarian, or breast cancers. Because the drug isn't water soluble, it's mixed into a solvent called eremophor, which can cause severe allergic reactions and is responsible for many of the treatment's side effects.

To create an alternative delivery system, chemist Eugene Zubarev and his graduate students at Rice University in Houston turned to particles of gold just 2 nanometers wide. Once injected into the bloodstream, the drug-loaded spheres should automatically accumulate in the tumor, says Zubarev.

That's because cancerous tumors are surrounded by leaky blood vessels with large pores. "When you inject a particle that is smaller than the average size of those holes, the particles will primarily end up inside that tumor," says Zubarev. Furthermore, the nanoparticles are small enough to avoid detection by the immune system.

The trick was to figure out how to attach paclitaxel to gold without affecting the drug's activity. The drug molecule has three sites that can serve as anchors. The so-called 2-prime site binds to support structures inside cells called microtubules, stopping the cells from dividing. Scientists have used the 2-prime site to attach paclitaxel to a variety of drug carriers, but then a second chemical is needed to cleave the drug from the carrier once the combination has entered a tumor cell.

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The Rice team used a different site on the drug. As they report in the Sept. 19 Journal of the American Chemical Society, the researchers first protected the 2-prime site by blocking it with a chemical attachment. Through a series of chemical steps, they then anchored the paclitaxel to the gold particles. Finally, they removed the protective chemical from the 2-prime site.

Using several techniques, the researchers determined that each particle carried about 70 molecules of paclitaxel. Knowing that number is critical for controlling dosage, says Zubarev. With other drug-delivery systems, it's often difficult to quantify how much drug is present.

Vincent Rotello, a chemist at the University of Massachusetts, Amherst, praises the team for the level of control that it achieved in coating the particles with paclitaxel. "If you have a system that's much more organized, it's easier to control the rate of release," he says.

Zubarev and his students have further modified their gold particles with a polymer to make them water soluble, and they're currently testing the drug-loaded particles in cells.