July 3, 2006
Buckyball-Antibody Combination Delivers Antitumor Drugs
Combining a monoclonal antibody known to target melanoma tumors with multiple C60 buckyballs, researchers at Rice University and the University of Texas M. D. Anderson Cancer Center have developed a new way to deliver multiple drugs simultaneously to tumors. Unlike other methods that use multiple targeting agents, such as antibodies, to deliver individual drug-loaded nanoparticles to malignant cells, this new approach attaches multiple nanoparticles to an individual tumor-targeting antibody.
In research published in the journal Chemical Communications, Lon Wilson, Ph.D., and colleagues at Rice University, working with Michael Rosenblum, Ph.D., and collaborators at The M. D. Anderson Cancer Center, describe the methods they used to attach as many as 40 water-soluble buckyballs onto a single antibody known as ZME-018. The M. D. Anderson Cancer Center investigators had already shown that ZME-018, which binds to a tumor protein known as gp240, will deliver anticancer drugs into melanoma tumors, while the Rice group has been developing buckyballs as drug delivery agents.
One potential advantage of attaching multiple nanoparticles to a single antibody is that it may be possible to load a different anticancer drug into each nanoparticle. "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 Wilson. "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."
While it's possible to attach drug molecules directly to antibodies, researchers have not 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.
The investigators originally had planned to overcome this limitation by attaching multiple molecules of the anticancer agent paclitaxel to each buckyball, which would then be connected chemically to the antibodies. To the team members’ surprise, many more buckyballs than expected attached themselves to the antibody. Moreover, the buckyballs stuck tightly to the antibodies without the need to form chemical bonds, so the increased payload did not significantly change the targeting ability of the antibody.
This work is detailed in a paper titled, “Fullerene (C60) immunoconjugates: interaction of water-soluble C60 derivatives with the murine anti-gp240 melanoma antibody.” This paper was published online in advance of print publication. An abstract of this paper is available at the journal’s website.