PLASTIC ANTIBODIES TARGET PEPTIDE - C&EN Global Enterprise

May 10, 2010 - The Irvine team, working with the group of Naoto Oku at the University of Shizuoka, in Japan, injected a lethal dose of melittin into m...
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PLASTIC ANTIBODIES TARGET PEPTIDE NANOTECHNOLOGY: Molecularly imprinted nanoparticles remove bee toxin from blood COU RT ESY O F K EN N ET H SHEA

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OLECULARLY 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, thereby 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

In this fluorescence image of the biodistribution of melittin and MIP nanoparticles in a mouse, the complex collects in the liver (inset). Violet is the lowest level and red is the highest.

VIRGINIA PROBES CLIMATE SCIENCE INVESTIGATION: Attorney general has gone too far, research supporters and critics agree

S CARRIE DEVORAH/WENN.COM/NEWSCOM

Cuccinelli is scrutinizing climate science for possible fraud.

CIENTISTS—and critics—of climate researcher

Michael E. Mann are pushing back against the Virginia attorney general’s probe into possible fraud connected with five grants Mann received while at the University of Virginia. Attorney General Kenneth T. Cuccinelli II is ordering UVA to turn over data and e-mails associated with those grants. Mann, a geophysicist, developed the once hotly contested “hockey stick” graph of historical temperature fluctuations over the past millennium. Now director of Pennsylvania State University’s Earth System Science Center, Mann is also one of the climate scientists whose controversial e-mails were made public in late 2009 (C&EN, Dec. 21, 2009, page 11). Mann received the grants, together worth $484,875, while working at UVA between 1999 and 2005, according to Cuccinelli’s late-April order issued under the Virginia Fraud Against Taxpayers Act. Three of the grants were sponsored by the National Oceanic & Atmospheric Administration, one was from the National Science WWW.CEN-ONLINE.ORG

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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 to 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, UrbanaChampaign, 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 antibodies are used,” he adds.—CELIA ARNAUD

Foundation, and another came from UVA’s Fund for Excellence in Science & Technology. The Union of Concerned Scientists (UCS) and, independently, some of the harshest critics of Mann’s research say Cuccinelli should back off. For instance, Stephen McIntyre, a prominent critic of Mann’s work and editor of the blog “Climate Audit,” which analyzes climate data, condemned Cuccinelli’s action as “a repugnant piece of over-zealousness.” “The notion of labeling controversial scientific findings as ‘fraudulent’ is extremely troubling,” says Francesca T. Grifo, director of the UCS Scientific Integrity Program. “Disagreement among scientists—to say nothing of disagreements between scientists and politicians—is simply not the same thing as fraud.” Mann stands by his results, telling C&EN that independent of where he has worked “all of my data and research methods are available in the public domain.” A recent Penn State investigation cleared Mann of misconduct allegations related to the e-mail controversy. Cuccinelli, a conservative Republican, is opposed to action to curb climate change, contending that it will harm the economy. Shortly after taking office in January, he petitioned the Environmental Protection Agency to reconsider its decision to regulate greenhouse gas emissions. He plans to sue the agency over federal greenhouse gas emission standards for vehicles. UVA says it intends to respond to Cuccinelli’s order. It has until May 27 to produce the requested materials.—CHERYL HOGUE AND STEVE RITTER

MAY 10, 2010