title: Impact of protein pre-coating on the protein corona composition and nanoparticle cellular uptake.
abstract: Nanoparticles (NPs) are functionalized with targeting ligands to enable selectively delivering drugs to desired locations in the body. When these functionalized NPs enter the blood stream, plasma proteins bind to their surfaces, forming a protein corona that affects NP uptake and targeting efficiency. To address this problem, new strategies for directing the formation of a protein corona that has targeting capabilities are emerging. Here, we have investigated the feasibility of directing corona composition to promote targeted NP uptake by specific types of cells. We used the well-characterized process of opsonin-induced phagocytosis by macrophages as a simplified model of corona-mediated NP uptake by a desired cell type. We demonstrate that pre-coating silica NPs with gamma-globulins (γ-globulins) produced a protein corona that was enriched with opsonins, such as immunoglobulins. Although immunoglobulins are ligands that bind to receptors on macrophages and elicit phagocytois, the opsonin-rich protein corona did not increase NP uptake by macrophage RAW 264.7 cells. Immunolabeling experiments indicated that the binding of opsonins to their target cell surface receptors was impeded by other proteins in the corona. Thus, corona-mediated NP targeting strategies must optimize both the recruitment of the desired plasma proteins as well as their accessibility and orientation in the corona layer.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Vahid
authors.initials: V
authors.lastname: Mirshafiee
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Raehyun
authors.initials: R
authors.lastname: Kim
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Soyun
authors.initials: S
authors.lastname: Park
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Cardiovascular Institute, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Nanotechnology Research Center and Department of Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: mahmoudi@stanford.edu.
authors.forename: Morteza
authors.initials: M
authors.lastname: Mahmoudi
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: mlkraft@illinois.edu.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Kraft
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis; D005434:Flow Cytometry; D006801:Humans; D057446:Hydrodynamics; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D000066970:Protein Corona; D000067996:RAW 264.7 Cells; D011961:Receptors, Fc / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry*; D055672:Static Electricity; D053719:Tandem Mass Spectrometry; D005719:gamma-Globulins / Q000737:chemistry*
chemical_list: D000066970:Protein Corona; D011961:Receptors, Fc; D012709:Serum Albumin; D005719:gamma-Globulins
keywords: Fc receptor; Immunoglobulins; Nanoparticle; Opsonins; Protein corona; Targeted delivery