Fullerene Find Promising for Medical Use

Fullerene Find Promising for Medical Use

BY LIA UNRAU
Rice News Staff
June 25, 1998

Rice researchers recently conducted the first detailed biological study showing
what happens to carbon fullerene material–the buckyball and its relatives–in
animal bodies, proving that fullerenes with radioactive metals inside can be
cleared from the body.

The find lends promise to developing fullerenes–hollow, cagelike carbon molecules
discovered at Rice in 1985–for use in medical applications such as nuclear
medicine and drug delivery.

Using a rugby-shaped ball of a C82 fullerene containing radioactive holmium
atoms, Rice chemist Lon Wilson and graduate student Dawson Cagle created a radiotracer
similar to those that doctors use to image patients’ diseased organs or kill
cancerous tumors. They injected the material into mice and rats and observed
where it went, how long it stayed there and how it cleared from the body.

The researchers made the fullerene material water-soluble by putting hydroxy
chemical groups on the surface of the metallofullerenes to make them resemble
"stealth liposomes," which are materials invisible to the immune system.

"This work shows that fullerene materials can be engineered to do their
work and be cleared from the body," Wilson says. The material cleared from
the blood, was not toxic, did not react with the body and was specifically attracted
to bone tissue. These qualities make fullerenes and metallofullerenes worth
pursuing as new medical materials, Wilson and Cagle say.

The Rice chemists saw clearance of about 20 percent of the material over a
five-day period in rats. The next step will be to pursue methods to improve
upon the clearance. "The door is now open to see how well we can encourage
clearance as well as the targeting of specific tissue," Wilson says.

Theirs is the first detailed study of metallofullerenes in animal subjects,
studying distribution of the material in mice and its metabolism in rats. The
research was presented at the national meeting of the American Chemical Society
in March and the Fullerene Symposium of the Electrochemical Society in San Diego
in May.

Wilson and Cagle showed that radioactive fullerenes stay in the blood for over
an hour, an advantage for imaging the circulatory system. They also showed that
the material localizes in the spleen, kidneys and liver, but with slow and steady
clearance.

Another advantage of a metallofullerene is that the radioactive metal is trapped
inside the carbon shell, which is very stable and resistant to metabolism by
the body. Wilson suspects that the fullerene cages remain intact throughout
the process and do not release toxic metals in the body. Materials currently
used can break down after an hour and some amount of their toxic metals can
be released into the body.

The metallofullerenes showed slow clearance from all tissue except in bone,
where it steadily increased with time, a totally unexpected result, according
to Wilson. Says Cagle, "In theory, it is possible that we could selectively
target bone tissue for delivery of drugs, for instance, to treat leukemia, bone
cancer and bone pain."

Wilson also notes: "Commercial development of fullerene products has been
hampered by the cost of fullerenes, but medical applications will tolerate higher
cost, especially for unique benefits when only very small amounts of material
are needed per dose. We are very encouraged by our early results and believe
that fullerene materials could be the basis of many new designer drugs of the
21st century."

Research collaborators include Michael Alford of TDA Research Inc. in Wheat
Ridge, Colo., Stephen Kennel and Saed Mirzadeh at the Oak Ridge National Laboratory
in Oak Ridge, Tenn.; and Gary Ehrhardt of the University of Missouri.

For related information visit the following Web sites:
The Department of Chemistry: http://pchem1.rice.edu/dept.html
The Center for Nanoscale Science and Technology: http://cnst.rice.edu/