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UCI Researchers Use Nanoparticles for First Plastic Antibodies

by Editor1 last modified July 20, 2010 - 20:46

University of California Irvine researchers have developed the first "plastic antibodies," nanoscale polymeric particles used to stop the spread of bee venom through the bloodstream of mice. The polymer nanoparticles were prepared by "molecular imprinting."

UCI Researchers Use Nanoparticles for First Plastic Antibodies

The polymer nanoparticles were prepared by "molecular imprinting" a technique UCI researchers Prof. Kenneth Shea and project scientist Yu Hoshino compared to plaster casting.

UCI researchers Prof. Kenneth Shea and project scientist Yu Hoshino compared the technique to plaster casting -- at the nanoscale. The antibodies were designed to match and encase melittin, a peptide in bee venom that causes cells to rupture, which can lead to organ failure or death.

The researchers linked melittin with small molecules called monomers, solidifying the two into a network of long polymer chains. After the plastic hardened, they removed the melittin, leaving nanoparticles with minuscule melittin-shaped holes.

When injected into mice previously given high doses of melittin, the now-precisely imprinted nanoparticles enveloped the matching melittin molecules, "capturing" them before they could do damage.

"Never before have synthetic antibodies been shown to effectively function in the bloodstream of living animals," Shea reported. "This technique could be utilized to make plastic nanoparticles designed to fight more lethal toxins and pathogens."

Other contributors included Takashi Kodama of Stanford University and Hiroyuki Koide, Takeo Urakami, Hiroaki Kanazawa and Naoto Oku of Japan's University of Shizuoka. The study was published in the Journal of the American Chemical Society.

Unlike natural antibodies produced by live organisms and harvested for medical use, synthetic antibodies can be created in the lab at a lower cost and have a longer shelf life.

Shea also described the success of the project, noting "The bloodstream includes a sea of competing molecules – such as proteins, peptides and cells – and presents considerable challenges for the design of nanoparticles," Shea said. "The success of this experiment demonstrates that these challenges can be overcome."

Inside ‘Molecular Imprinting’
The Value of Nanoscale Templates
The term "molecular imprinting," like gene imprinting, creates template-shaped cavities in polymer matrices with memory of the template molecules to be used in molecular recognition, according to listings in Wikipedia.

The technique is based on the system used by enzymes for substrate recognition, which is called the "lock and key" model. The active binding site of an enzyme has a unique geometric structure that is particularly suitable for a substrate. A substrate that has a corresponding shape to the site is recognized by selectively binding to the enzyme, while an incorrectly shaped molecule that does not fit the binding site is not recognized.

In a similar way, molecularly imprinted materials are prepared using a template molecule and functional monomers that assemble around the template and subsequently get cross-linked to each other.

The functional monomers, which are self-assembled around the template molecule by interaction between functional groups on both the template and monomers, are polymerized to form an imprinted matrix (commonly known in the scientific community as a molecularly imprinted polymer i.e. MIP).

Then the template molecule is removed from the matrix under certain conditions, leaving behind a cavity complementary in size and shape to the template. The obtained cavity can work as a selective binding site for a specific template molecule.