Altered buckyballs go straight to bone.

Scientists are one step closer to using fullerenes--spherical carbon molecules-to deliver powerful drugs straight to diseased tissues. Direct delivery can increase drugs' potency while reducing their harmful side effects.

Unlike other molecules that are used to encapsulate drugs, fullerenes resist breakdown by the body. This stability is especially important for holding compounds that would cause harm if released in healthy cells. For example, some cancer therapies attack tumors with compounds containing radioactive metal atoms. If the metals escape from their molecular capsules before they arrive at their targets, the stray radiation can damage normal tissue.

Kelly A. Gonzalez and Lon J. Wilson of Rice University in Houston have modified 60-carbon fullerenes, called buckyballs, to home in on bone when injected into the body. Wilson presented the findings this week at a meeting of the Electrochemical Society in Seattle.

"The traditional way to target tissues is with antibodies," complex molecules that seek out specific proteins on cell surfaces, says Stephen R. Wilson of New York University, who also studies the medical applications of fullerenes. The Rice scientists' design of a simple molecule that chemically attaches to a particular tissue is "the kind of thing that a lot of people are trying to do."

Gonzalez and Wilson designed their compound to stick to a bone mineral called hydroxyapatite. They attached a chemical group called an amide bisphosphonate to a buckyball and then added 16 hydroxyls to make the molecule water-soluble. The bisphosphonate binds to hydroxyapatite, and the fullerene compound interferes with the mineral's crystal growth.

While this effect might be undesirable in a therapeutic treatment, it offers a way to determine whether the molecule sticks to bone. Hydroxyapatite-crystal formation releases tiny amounts of hydrochloric acid. Wenju Wu and George H. Nancollas of the State University of New York at Buffalo earlier developed a technique to measure how well compounds adhere to bone by detecting this acid.

Together, the SUNY and Rice scientists found that in a test tube, the new compound reduces the rate of hydroxyapatite formation, indicating that the modified buckyballs bind well to bone.

They also got a surprise when characterizing the compound: The molecule has one unpaired electron, making it magnetic. "This is a very curious beast," says Lon Wilson. This property makes the compound a potential contrast agent for magnetic resonance imaging (MRI). A contrast agent injected into a patient can sharpen an MRI picture, revealing otherwise invisible features.

In the April 27 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, Lon Wilson and his coworkers also report on rat studies showing that water-soluble buckyballs containing a radioactive atom build up in bone but are slowly cleared out of other tissues. Such excretion has "never been seen for a fullerene material before," he says. It's crucial to demonstrate that fullerenes can be flushed out of the body before they're developed into drugs, he adds.