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Study Explains How Drug Carriers Interact with Immune System

By BiotechDaily International staff writers
Posted on 20 Apr 2017
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Image: Circulating white blood cells, commonly referred to as leukocytes (large yellow clusters), can be seen lining an inflamed vessel wall along with leukosomes (small yellow speckles). Leukosomes, designed to mimic white blood cells, go unnoticed as they accumulate at the inflamed vessel (purple background), allowing them to concentrate their therapeutic payload at the target site (Photo courtesy of Houston Methodist Hospital).
Image: Circulating white blood cells, commonly referred to as leukocytes (large yellow clusters), can be seen lining an inflamed vessel wall along with leukosomes (small yellow speckles). Leukosomes, designed to mimic white blood cells, go unnoticed as they accumulate at the inflamed vessel (purple background), allowing them to concentrate their therapeutic payload at the target site (Photo courtesy of Houston Methodist Hospital).
Researchers seeking to develop nanoparticle-based drug delivery systems have determined how a specialized class of nanoparticles called leukosomes avoids immune system response in a mouse model system.

Understanding interactions occurring at the interface between nanoparticles and biological components is an urgent challenge in nanomedicine due to their effect on the biological fate of the nanoparticles. After the systemic injection of nanoparticles, a protein corona constructed by blood components surrounds the carrier’s surface and modulates its pharmacokinetics and biodistribution. Immune cells such as leukocytes freely circulate in blood vessels, recognize inflammation, and accumulate in inflamed tissues. They do so by using special receptors and ligands on their surface.

Investigators at Houston Methodist Hospital had previously purified leukocytes from a patient and then integrated their special ligands and receptors into the surface of liposome-like particles, which they called leukosomes. Using the body’s own materials, they built a drug delivery system camouflaged as the body’s own defense system. Leukosomes were able to target inflamed tissues because they retained the same surface properties of the immune cell membranes from which they are made.

In the current study, the investigators studied leukosomes' nanoparticle protein corona in vivo. They described in the March 6, 2017, online edition of the journal ACS Nano a time-dependent quantitative and qualitative analysis of the protein corona adsorbed in vivo on leukosomes and control liposomes. They observed that leukosomes absorbed fewer proteins than liposomes and identified a group of proteins specifically adsorbed on leukosomes. It was felt that the presence of macrophage receptors on leukosomes’ surface neutralized their protein corona-meditated uptake by immune cells.

“Now we have a clearer understanding of how to use our leukosomes to evade those immune cells and prevent the body’s inflammatory response,” said senior author Dr. Ennio Tasciotti, director of the center for biomimetic medicine at Houston Methodist Hospital. “We have known overactive immune cells can behave like Pac Men, gobbling up the nanoparticles and ridding the body of these "foreign invaders" before they reach the intended target.”


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