Nanoparticles Designed to Target Inflammation

Author:  Maria Zagorulya

Institution:  University of Rochester

Like preschoolers looking for minute differences between two similar pictures on a worksheet, scientists have been working on differentiating between active and inactive neutrophils involved in the immune response. Only recently, researchers at the University of Illinois at Chicago have created anti-inflammatory drugs targeted specifically at active neutrophilic cells that have gone out of control.

Neutrophils are the most common type of white blood cells. They participate in the normal immune response by binding to the site of injury on a blood vessel and engulfing any potential infection-causing microorganisms from the damaged tissue. When the immune system overreacts however, the neutrophils begin to accumulate at the injury site, adhering to blood vessel walls which causes further tissue damage and chronic inflammation.

Together with his colleagues, Asrar B. Malik, the Schweppe Family Distinguished Professor and head of pharmacology in the UIC College of Medicine, identified a receptor found on the activated neutrophils engaged in the immune response but not on the inactive neutrophils circulating in the bloodstream. The scientists designed a nanoparticle, which carries an anti-inflammatory drug called piceatannol and binds specifically to this receptor. By labeling nanoparticles with a fluorescent dye, Malik and colleagues were able to observe specificity of particle binding in real-time through intra-vital microscopy in mice with induced vascular inflammation.

Previous treatments involving corticosteroids and non-steroidal anti-infammatory drugs affected the whole body and had serious side effects. However, this new development is very target specific.

"The nanoparticle is very much like a Trojan horse,” Malik remarks. “It binds to a receptor found only on these activated, sticky neutrophils, and the cell automatically engulfs whatever binds there. Because circulating neutrophils lack these receptors, the system is incredibly precise and targets only those immune cells that are actively contributing to inflammatory disease."

Once delivered, piceatannol then acts upon the out-of-control neutrophils, preventing their adhesion to other cells and thus reducing inflammation.

These findings published in Nature Nanotechnology have applications in treatment of various inflammatory diseases, including acute lung injury, which has a 50% mortality rate if left untreated. It looks like the skills we learn in kindergarten really are useful in the adult world, or at least in the world of science.