Molecularly imprinted polymeric (MIP) nanoparticles can act as "plastic antibodies" to neutralize toxins in live animals, according to a new study (J. Am. Chem. Soc., DOI: 10.1021/ja102148f).
Chemists Kenneth J. Shea and Yu Hoshino of the University of California, Irvine, and coworkers developed MIP nanoparticles that target the peptide melittin, a component of bee venom that breaks open cells and causes them to release their contents. At high enough doses, melittin can lead to kidney failure and death.
The researchers make the nanoparticles by polymerizing various acrylamide monomers in the presence of melittin and then removing the template, creating binding sites for the target molecule. The approach is called molecular imprinting.
The Irvine team, working with the group of Naoto Oku at the University of Shizuoka, in Japan, injected a lethal dose of melittin into mice. Animals that then immediately received an injection of the melittin-targeting MIP nanoparticles showed a significantly higher survival rate than those that did not receive the nanoparticles. Although the MIP nanoparticles have previously been shown to target melittin in vitro with an affinity and selectivity comparable with those of natural antibodies (J. Am. Chem. Soc. 2008, 130, 15242), this is the first time the synthetic antibodies have been used in living animals.
"This is an excellent demonstration of the potential for molecularly imprinted nanoparticles to selectively bind peptides and related targets in the complex environment found in the bloodstream," says Steven C. Zimmerman of the University of Illinois, Urbana-Champaign, who also studies synthetic antibodies.
The nanoparticles show minimal toxicity, Shea says. The researchers determined the biodistribution of both the melittin and the MIP nanoparticles by fluorescence imaging of dye-labeled nanoparticles and melittin. The MIP nanoparticles and their targeted melittin accumulated in the same cells in the liver, suggesting that the nanoparticles sequester the toxin and that the complex is then cleared from the body by the liver.
Such nanoparticles could be fabricated for a variety of targets, Shea says. "This opens the door to serious consideration for these nanoparticles in all applications where proteins are used," he adds.