Researchers at the University of Pennsylvania School of Medicine have developed a new coating for nanoparticles that may help protect them from immune system attacks. The approach, which uses naturally occurring proteins that can inhibit the complement system, can significantly reduce the immune destruction of nanoparticles, meaning more can reach their target tissues. Aside from the potential to increase the effectiveness of nanotherapies, the coating may also be useful for medical devices such as stents and catheters.
Nanoparticles offer tremendous potential to deliver drugs or vaccines directly to the desired tissue, maximizing efficacy and reducing the potential for side effects. They are currently enjoying a bit of notoriety for their role in providing mRNA vaccines against COVID-19. However, such vaccines are delivered directly into a muscle, where they are protected from the worst devastation of the immune system. The bloodstream can be a fairly hostile environment for systemically administered nanoparticles.
One of the main problems is complement proteins, which can swarm unprotected nanoparticles into the bloodstream, leading to inflammation, phagocytosis by white blood cells, and nanoparticle destruction. With many nanoparticle technologies, the amount that actually reaches the target tissue can be less than 1% of an administered dose, which represents very poor efficiency. Furthermore, in patients with severe inflammatory diseases, these nanoparticle-induced immune responses could exacerbate their symptoms and limit the safety of nanotherapies in these patient populations.
Researchers have worked to reduce this immune response to nanoparticles. A useful nanoparticle coating is polyethylene glycol, which typically reduces immune attack somewhat, but not completely. To improve this, the UPenn researchers developed a new method to coat these particles using a component of the immune system that antagonizes complement proteins. These naturally occurring anti-complement proteins are used by the body to protect its own cells from immune attack, and when the researchers coated nanoparticles with one of them, Factor I, it helped significantly increase complement protein binding to reduce.
So far, the research team has shown that the coated nanoparticles stay in the blood much longer, allowing more of them to reach the target tissue. The particles also failed to elicit serious immune responses in a mouse model of severe inflammatory diseases, suggesting they may be suitable for use in such patients.
Studies in Advanced Materials: Combating the deleterious effects of complement on nanomedicine by conjugating complement-regulating proteins to nanoparticles
