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Penn researchers develop protein 'passport' that help nanoparticles get past immune system
Date:2/21/2013

s, the researchers also attached antibodies of the type that could be used in targeting cancer cells or other kinds of diseased tissue. Beyond a proof of concept for therapeutics, these antibodies also served to attract the macrophages' attention and ensure the minimal peptide's passport was being checked and approved.

"We're showing that the peptide actually does inhibit the macrophage's response," Discher said. "We force the interaction and then overwhelm it."

The test of this minimal peptide's efficacy was in mice that were genetically modified so their macophages had SIRPa receptors similar to human. The researchers injected two kinds of nanoparticles ones carrying the peptide passport and ones without and then measured how fast the mice's immune system cleared them.

"We used different fluorescent dyes on the two kinds of nanoparticles, so we could take blood samples every 10 minutes and measure how many particles of each kind were left using flow cytometry," Rodriguez said. "We injected the two particles in a 1-to-1 ratio and 20-30 minutes later, there were up to four times as many particles with the peptide left."

Even giving therapeutic nanoparticles an additional half-hour before they are eaten by macrophages could be a major boon for treatments. Such nanoparticles might need to make a few trips through the macrophage-heavy spleen and liver to find their targets, but they shouldn't stay in the body indefinitely. Other combinations of exterior proteins might be appropriate for more permanent devices, such as pacemaker leads, enabling them to hide from the immune system for longer periods of time.

While more research is necessary before such applications become a reality, reducing the peptide down to a sequence of only a few amino acids was a critical step. The relative simplicity of this passport molecule to be more easily synthesized makes it a more attractive component for future therapeutics.

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Contact: elerner@upenn.edu
elerner@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert  

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