A new method to increase effectiveness of nanomedicines

Penn Medicine researchers have discovered a new, more effective way to prevent the body’s proteins from treating nanomedicines like foreign invaders by coating the nanoparticles with a coating to suppress the immune response that dampens the effectiveness of the therapy.

After being injected into the blood, nanomedicines (blue spheres) are immediately attacked by proteins in the immune system called complement proteins (orange). Complement proteins cause rapid destruction of nanomedicine and also trigger anaphylaxis-like reaction. By attaching complement-degrading proteins (yellow protein ninjas) to the surface of nanomedicines, Penn researchers have largely solved this problem, potentially allowing more diseases to be safely treated by nanomedicine. (Image: Penn Medicine News)

When injected into the bloodstream, unmodified nanoparticles are swarmed by elements of the immune system called complement proteins, triggering an inflammatory response and preventing the nanoparticles from reaching their therapeutic targets in the body. Researchers have developed a few methods to reduce this problem, but the Penn Medicine team, whose results are published in Advanced Materials, invented what may be the best method yet: coating nanoparticles with natural complement activation inhibitors.

Nanoparticles are tiny capsules, typically made of proteins or fat-related molecules, that serve as delivery vehicles for certain types of treatments or vaccines — usually those containing RNA or DNA. The best-known examples of nanoparticle-mediated drugs are mRNA vaccines against COVID-19.

“It turned out to be one of those technologies that just works right out of the box and better than expected,” says study co-author Jacob Brenner, associate professor of pulmonary medicine in the Department of Pulmonary, Allergy and Critical Care Medicine.

In the study, the research team developed an alternative or additional approach to protecting nanoparticles – an approach based on natural complement inhibitor proteins that circulate in the blood and attach to human cells to protect them from complement attacks.

The researchers found in laboratory experiments that coating standard PEG-protected nanoparticles with one of these complement inhibitors, called Factor I, provided dramatically better protection against complement attacks. In an animal model, the same strategy prolonged the half-life of standard nanoparticles in the bloodstream, allowing a much larger fraction of them to reach their targets.

“Many bacteria also coat with these factors to protect themselves from complement attacks, so we decided to borrow this strategy for nanoparticles,” says co-senior author Jacob Myerson, a senior research scientist in the Department of Systems Pharmacology and Translational Therapeutics .

Read more at Penn Medicine News.