Researchers at the University of Pennsylvania School of Medicine have created a new coating for nanoparticles that can help protect them from immune system attacks. The approach, which uses natural proteins that can inhibit the complement system, can significantly reduce the immune destruction of nanoparticles, which means they can further reach their target tissue. 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 great potential for delivering drugs or vaccines directly to the tissue of interest, maximizing efficacy and reducing the potential for side effects. They currently enjoy some fame for their role in the distribution of mRNA vaccines against COVID-19. However, these vaccines are introduced directly into a muscle, where they are protected from the worst damage of the immune system. For systemically administered nanoparticles, the bloodstream can be a fairly hostile environment.
One of the main problems is complement proteins, which can clump unprotected nanoparticles into the bloodstream, leading to inflammation, phagocytosis by white blood cells, and destruction of nanoparticles. For many nanoparticle technologies, the amount that actually reaches the target tissue may be less than 1% of a administered dose, which represents a very low efficiency. In addition, for patients with severe inflammatory disease, these nanoparticle-induced immune reactions could worsen their symptoms, limiting the safety of nanotherapies in these patient populations.
Researchers have been working to reduce this immune response to nanoparticles. A useful nanoparticle coating is polyethylene glycol, which usually reduces the immune attack a bit, but not completely. Seeking to improve it, UPenn researchers have developed a new way to coat these particles, using a component of the immune system that antagonizes complement proteins. The body uses these natural anti-complement proteins to protect its own cells from immune attack, and when the researchers coated nanoparticles with one of them, called Factor I, it helped significantly reduce complement protein binding.
So far, the research team has shown that coated nanoparticles last much longer in the blood, allowing more of them to reach the target tissue. The particles also did not elicit severe immune reactions in a mouse model of severe inflammatory disease, suggesting that they may be suitable for use in these patients.