Researchers at the University of Pennsylvania School of Medicine have created a new coating for nanoparticles that can help to protect them from attacks by the immune system. The approach, which uses naturally occurring proteins that can inhibit the complement system, can significantly reduce immune destruction of nanoparticles, meaning that more may 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 huge potential in delivering drugs or vaccines right to the tissue of interest, maximizing efficacy and reducing the potential for side-effects. They are currently enjoying a little fame for their role in delivering mRNA vaccines against COVID-19. However, such vaccines are delivered directly into a muscle, where they are protected from the worst ravages of the immune system. For systemically administered nanoparticles, the bloodstream can be a pretty hostile environment.
One of the major issues is complement proteins, which can swarm unprotected nanoparticles in the bloodstream, resulting in inflammation, phagocytosis by white blood cells and nanoparticle destruction. For many nanoparticle technologies, the amount that actually reaches the target tissue can be less than 1% of an administered dose, representing very poor efficiency. Moreover, for patients with severe inflammatory disease, these nanoparticle-induced immune reactions could exacerbate their symptoms, limiting the safety of nanotherapies in these patient populations.
Researchers have been working to reduce this immune reaction to nanoparticles. One useful nanoparticle coating is polyethylene glycol, which typically reduces the immune attack somewhat, but not completely. Looking to improve on this, the UPenn researchers have developed a new way 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, called Factor I, it helped to significantly reduce complement protein binding.
So far the research team has shown that the coated nanoparticles last for a significantly longer time in the blood, allowing more of them to reach the target tissue. The particles also did not elicit serious immune reactions in a mouse model of severe inflammatory illness, suggesting they could be suitable for use in such patients.
Study in Advanced Materials: Combating Complement’s Deleterious Effects on Nanomedicine by Conjugating Complement Regulatory Proteins to Nanoparticles