Individual lifestyle exposure as a determinant for the formation of biomolecule corona on nanoparticles

PROJECT SUMMARY / ABSTRACT The proposed project aims to deliver a unique perspective to the process of non-specific adsorption of serum biomolecules on intravenously administered circulating nanoparticles. Nanoparticles are widely investigated for their ability to not only formulate water-insoluble or enzyme-degradable drugs into an injectable solution, but also target the encapsulated therapeutics to the tissue of interest. While the latter is mostly achieved via intentional modification of the nanoparticle’s surface, recent findings have reported the presence of serum proteins non- specifically adhered to the nanoparticle surface, a phenomenon termed protein corona, which redirects the nanoparticles to non-targeted tissues based on the composition of bound proteins. The identity and quantity of adsorbed proteins on nanoparticles is currently hypothesized to be determined primarily from specific physicochemical properties of the nanoparticle. However, with growing clinical and pre-clinical evidence of differential composition of metabolites and proteins in blood serum depending on different lifestyle exposure, such as stress-inducing events, there is an unmet need to evaluate the effect of various kinds and levels of serum biomolecules on the formation of characteristic corona around any given nanoparticle formulation. To fill in the gap, we will first utilize animal models with two different stress-related lifestyle exposures, mainly social isolation and overcrowding, to fully characterize differential biomolecular composition in blood serum (Aim 1). Then, we will use the same blood serum to incubate nanoparticles of defined properties, evaluate the biomolecular composition in the corona, and analyze its relationship to the initial metabolome and proteome profile in serum (Aim 2). Dr. Prokai will serve as a consultant and support the metabolomics and proteomics analyses of the blood serum as well as nanoparticle samples that the Kim group will prepare. This project brings in the complementary expertise of two research groups to generate a new perspective to the biocorona formation in intravenously administered nanoparticles, with the long-term goal of developing or selecting a personalized nanoparticle design to intentionally promote the formation of specific organ-targeting biocorona.