Houston,
June 21, 2006 – In the ongoing search for better
ways to target anticancer drugs to kill tumors without
making people sick, researchers find that nanoparticles
called buckyballs might be used to significantly
boost the payload of drugs carried by tumor-targeting
antibodies.
In research due to appear in an upcoming issue of
the journal Chemical Communications, scientists at
Rice University and The University of Texas M. D.
Anderson Cancer Center describe a method for creating
a new class of anti-cancer compounds that contain
both tumor-targeting antibodies and nanoparticles
called buckyballs. Buckyballs are soccer ball-shaped
molecules of pure carbon that can each be loaded
with several molecules of anticancer drugs like Taxol®.
In the new research, the scientists found they could
load as many as 40 buckyballs into a single skin-cancer
antibody called ZME-018. Antibodies are large proteins
created by the immune system to target and attack
diseased or invading cells.
Previous work at M. D. Anderson has shown that ZME-018
can be used to deliver drugs directly into melanoma
tumors, and work at Rice has shown that Taxol can
be chemically attached to a buckyball.
"The idea that we can potentially carry more than
one Taxol per buckyball is exciting, but the real
advantage of fullerene immunotherapy over other targeted
therapeutic agents is likely to be the buckyball's
potential to carry multiple drug payloads, such as
Taxol plus other chemotherapeutic drugs," said Rice's
Lon Wilson, professor of chemistry. "Cancer cells
can become drug resistant, and we hope to cut down
on the possibility of their escaping treatment by
attacking them with more than one kind of drug at
a time."
Researchers have long dreamed of using antibodies
like ZME-018 to better target chemotherapy drugs
like Taxol, and M. D. Anderson's Michael G. Rosenblum,
Ph.D., professor in the Department of Experimental
Therapeutics and Chief of the Immunopharmacology
and Targeted Therapy Laboratory, has conducted some
of the pioneering work in this field.
"This is an exciting opportunity to apply novel
materials such as fullerenes to generate targeted
therapeutics with unique properties," Rosenblum said. "If
successful, this could usher in a new class of agents
for therapy not only for cancer, but for other diseases
as well."
While it's possible to attach drug molecules directly
to antibodies, Wilson said scientists haven't been
able to attach more than a handful of drug molecules
to an antibody without significantly changing its
targeting ability. That happens, in large part, because
the chemical bonds that are used to attach the drugs
-- strong, covalent bonds -- tend to block the targeting
centers on the antibody's surface. If an antibody
is modified with too many covalent bonds, the chemical
changes will destroy its ability to recognize the
cancer it was intended to attack.
Wilson said the team from Rice and M. D. Anderson
had planned to overcome this limitation by attaching
multiple molecules of Taxol to each buckyball, which
would then be covalently connected to the antibodies.
To the team's surprise, many more buckyballs than
expected attached themselves to the antibody. Moreover,
no covalent bonds were required, so the increased
payload did not significantly change the targeting
ability of the antibody.
Wilson said certain binding sites on the antibody
are hydrophobic (water repelling), and the team believes
that these hydrophobic sites attract the hydrophobic
buckyballs in large numbers so multiple drugs can
be loaded into a single antibody in a spontaneous
manner to give the antibody-drug agent more "bang
for the buck."
"The use of these nanomaterials solves some intractable
problems in targeted therapy and additionally demonstrates
the increasing value of the team science approach
bridging different disciplines to uniquely address
existing problems," Rosenblum said.
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