

Dmitri Simberg Dmitri Simberg Previously, the lab of CU Cancer Center investigator Dmitri Simberg, PhD, has shown that blood proteins (collectively called protein corona) coat nanoparticles, marking them for immune system attack. In particular, the Simberg lab showed that one of the most important components of the immune system, namely the complement system, cannot attack nanoparticles unless they are coated with protein corona. Now the Simberg lab shows another step in this process: Natural antibodies within the protein corona are responsible for the ability of the complement system to recognize and attack nanoparticles.



"Basically, we found that C3 deposition on nanoparticles (and thus immune system activation against nanoparticles) really depends on natural antibodies in each person's blood," says Simberg, who is also an associate professor in the Skaggs School of Pharmacy and Pharmaceutical Sciences. "We can remove these antibodies and there is very little complement system activation. Then we can add these antibodies back and there is activation.



The study, which was done in collaboration with Moein Moghimi, PhD, Professor at Newcastle University in the UK, looked at the ability of a prevalent complement system protein, known as C3, to find and attack widely used nanoparticle-based anti-cancer pharmaceuticals LipoDox and Onivyde, (as well as the nanoparticle-based iron oxide supplement Feraheme). When Simberg and colleagues depleted antibodies known as immunoglobulins from blood of healthy donors and cancer patients, the ability of C3 to find and mark these nanoparticles was reduced 70-95 percent. When the team restored immunoglobulins, they again saw C3 buildup on these nanomedicines.