Delivery success rate of engineered nanoparticles in the presence of the protein corona: a systems-level screening

Nanoparticles (NPs) for medical applications are often introduced into the body via intravenous injections, leading to the formation of a protein corona on their surface due to the interaction with blood plasma proteins. Depending on its composition and time evolution, the corona will modify the biological behavior of the particle. For successful delivery and targeting, it is therefore important to assess on a quantitative basis how and to what extent the presence of the corona perturbs the specific interaction of a designed NP with its cellular target. We present a theoretical systems-level analysis, in which peptides have been covalently coupled to the surface of nanoparticles, describing the delivery success rate in varying conditions, with regard to protein composition of the surrounding fluid. Dynamic modeling and parameter sensitivity analysis proved to be useful and computationally affordable tools to aid in the design of NPs with increased success rate probability in a biological context. FROM THE CLINICAL EDITOR: The formation of a protein corona consisting of blood plasma proteins on the surface of intravenously delivered nanoparticles may modify the biological behavior of the particles. This team of investigators present a theoretical systems-level analysis of this important and often neglected phenomenon