Injection of nanoparticles into the body triggers an inflammatory response caused by blood components accumulating on their surface. Now, a team of nanomedicine and regenerative medicine scientists have described how specially-engineered nanoparticles (leukosomes) injected into mice can prevent the formation of a layer of biomolecules, called the protein corona, around their surface.

The body’s natural defense response to the formation of this protein is to filter out the foreign objects, in this case the nanoparticles. The presence of immune system regulators, known as macrophage receptors, on the surface of the leukosomes improved the amount of time these nanoparticles remained in the body to reach their target.

In a 2016 study, Ennio Tasciotti, Ph.D, senior author and director of the Center for Biomimetic Medicine at Houston Methodist Research Institute and team created these leukosomes and evaluated their ability to treat localized inflammation. Leukosomes are able to target inflamed tissues because their design mimics immune cell membranes.

Investigating Leukosomes

To provide more information on the properties of these leukosomes, the team decided to investigate their protein corona in vivo. Most of the insight previously gained into the protein corona was been obtained using in vitro experiments, which have been shown to only minimally reproduce in vivo phenomena.

“Now we have a clearer understanding of how to use our leukosomes to evade those immune cells and prevent the body’s inflammatory response,” Tasciotti said. “We’ve 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."

Learning how to treat inflammation by overcoming the body’s own defense mechanisms may lead to broader applications for treating diseases characterized by inflammation such as cancer, cardiovascular and autoimmune diseases.

While this latest research helps to improve understanding of the overall properties of leukosomes, further studies are needed to confirm the benefits to patients and ways to prevent the human body from rejecting targeted therapies.

Claudia Corbo, Roberto Molinaro, Francesca Taraballi, Naama E. Toledano Furman, Kelly A. Hartman, Michael B. Sherman, Enrica De Rosa, Dickson K. Kirui, Francesco Salvatore, and Ennio Tasciotti Unveiling the in Vivo Protein Corona of Circulating Leukocyte-like Carriers ACS Nano 2017 11 (3), 3262-3273 DOI: 10.1021/acsnano.7b00376

Image: Circulating white blood cells, commonly known as leukocytes (large yellow clusters), lining an inflamed vessel wall along with leukosomes (small yellow speckles). Credit: Houston Methodist

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