Plastic Antibodies Fight Toxins

Polymers that mimic the body's natural defenses could be a new class of inexpensive therapeutics.

For the first time, researchers have shown that a nonbiological molecule called a plastic antibody can work just like a natural antibody. In animal tests, the plastic particles bind to and neutralize a toxin found in bee stings; the toxin and antibody are then cleared to the liver, the same path taken by natural antibodies. Researchers are now developing plastic antibodies for a wider range of disease targets in hopes of broadening the availability of antibody therapies, which are currently very expensive.

Toxic target: The toxin melittin, labeled purple in these fluorescent images, spreads throughout the body of an untreated mouse, shown at bottom. The mouse at top has been injected with an artificial antibody, also fluorescently labeled, that binds to the toxin and takes it to the liver. The spread of the toxin throughout the treated mouse’s body is also more limited, which is why less of its body appears purple in this image. Credit: Kenneth Shea

For more than 20 years, biochemists have attempted to mimic antibodies' ability to zero in on their targets, as part of a strategy to make more effective and cheaper therapeutics and diagnostics. "Though antibodies are produced on an industrial scale today because they're so important, the cost is very, very high," says Kenneth Shea, professor of chemistry at the University of California, Irvine. That's because antibodies are grown in animals; they're complex molecules that can't be made in a test tube, or even by bacteria. And antibodies, like other proteins, are very fragile. Even under refrigeration, they last just months. The question Shea and others have asked for 20 years, he says, is "would it be possible to design them from inexpensive, abiotic starting materials?" Such plastic antibodies could be made cheaply and then sit on the shelf, in theory, for years.

In 2008, Shea's group, working with researchers from the Tokyo Institute of Technology, demonstrated for the first time that plastic antibodies made using a technique called molecular imprinting could bind to a target as strongly and specifically as natural antibodies. Molecular imprinting involves synthesizing a polymer in the presence of a target molecule. The polymer grows around the target, "imprinting" it with the target's shape. It's analogous to making a plaster cast of one's hand, says Shea.

Story continues below

Looking to the properties of natural antibodies, Shea's group tailored the method for making polymers that more specifically target large proteins in biological solutions. Antibodies and their targets fit together like a key in a lock, or like a hand into a plaster cast. But they are also bound to their targets by chemistry and attracted by electrical interactions. Shea's methods involve looking to the properties of the target molecule and selecting starting materials that have an affinity for that target--in this case the protein melittin, the toxin in bee stings. At the same time, the method screens for starting materials that are not attracted to other, more common blood proteins. And the group took care to make the plastic antibody smaller than previous molecularly imprinted polymers, which were too big to be recognized by the body.