Researchers at Penn Medicine have discovered a new, more effective method of preventing the body’s own proteins from treating nanomedicines like foreign invaders, by covering the nanoparticles with a coating to suppress the immune response that dampens the therapy’s effectiveness.
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 devised some methods to reduce this problem, but the Penn Medicine team, whose findings are published in Advanced Materials, has invented what may be the best method yet: coating nanoparticles with natural suppressors of complement activation.
Nanoparticles are tiny capsules, typically engineered from proteins or fat-related molecules, that serve as delivery vehicles for certain types of treatment or vaccine—usually those containing RNA or DNA. The best-known examples of nanoparticle-delivered medicines are mRNA vaccines against COVID-19.
“It turned out to be one of those technologies that just works right away and better than anticipated,” says study co-senior author Jacob Brenner, an associate professor of pulmonary medicine in the Division of Pulmonary, Allergy, and Critical Care.
In the study, the research team came up with an alternative or add-on approach to protect nanoparticles—an approach based on natural complement-inhibitor proteins that circulate in the blood, attaching to human cells to help protect them from complement attack.
The researchers found that, in lab-dish experiments, coating standard PEG-protected nanoparticles with one of these complement inhibitors, called Factor I, provided dramatically better protection from complement attack. 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 themselves with these factors to protect against complement attack, so we decided to borrow that 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.