title: From the Cover: Disease-Induced Disparities in Formation of the Nanoparticle-Biocorona and the Toxicological Consequences.
abstract: Nanoparticle (NP) association with macromolecules in a physiological environment forms a biocorona (BC), which alters NP distribution, activity, and toxicity. While BC formation is dependent on NP physicochemical properties, little information exists on the influence of the physiological environment. Obese individuals and those with cardiovascular disease exist with altered serum chemistry, which is expected to influence BC formation and NP toxicity. We hypothesize that a BC formed on NPs following incubation in hyperlipidemic serum will result in altered NP-BC protein content, cellular association, and toxicity compared to normal serum conditions. We utilized Fe3O4 NPs, which are being developed as MRI contrast and tumor targeting agents to test our hypothesis. We used rat aortic endothelial cells (RAECs) within a dynamic flow in vitro exposure system to more accurately depict the in vivo environment. A BC was formed on 20nm PVP-suspended Fe3O4 NPs following incubation in water, 10% normal or hyperlipidemic rat serum. Addition of BCs resulted in increased hydrodynamic size and decreased surface charge. More cholesterol associated with Fe3O4 NPs after incubation in hyperlipidemic as compared with normal serum. Using quantitative proteomics, we identified unique differences in BC protein components between the 2 serum types. Under flow conditions, formation of a BC from both serum types reduced RAECs association of Fe3O4 NPs. Addition of BCs was found to exacerbate RAECs inflammatory gene responses to Fe3O4 NPs (Fe3O4-hyperlipidemic > Fe3O4-normal > Fe3O4) including increased expression of IL-6, TNF-α, Cxcl-2, VCAM-1, and ICAM-1. Overall, these findings demonstrate that disease-induced variations in physiological environments have a significant impact NP-BC formation, cellular association, and cell response.
authors.affiliation: *Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045;
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Shannahan
authors.affiliation: *Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045;
authors.forename: Kristofer S
authors.initials: KS
authors.lastname: Fritz
authors.affiliation: Department of Physics and Astronomy, Clemson University, Clemson, South Carolina, 29634; Clemson Nanomaterials Center and COMSET, Clemson University, Anderson, South Carolina, 29625.
authors.forename: Achyut J
authors.initials: AJ
authors.lastname: Raghavendra
authors.affiliation: Department of Physics and Astronomy, Clemson University, Clemson, South Carolina, 29634; Clemson Nanomaterials Center and COMSET, Clemson University, Anderson, South Carolina, 29625.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Podila
authors.affiliation: *Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045;
authors.forename: Indushekar
authors.initials: I
authors.lastname: Persaud
authors.affiliation: *Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045; jared.brown@ucdenver.edu.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Brown
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058185:Magnetite Nanoparticles
keywords: darkfield microscopy; endothelial cell; hyperlipidemia; iron oxide nanoparticles; nanotoxicology; protein corona.; proteomics