title: Complement proteins bind to nanoparticle protein corona and undergo dynamic exchange in vivo.
abstract: When nanoparticles are intravenously injected into the body, complement proteins deposit on the surface of nanoparticles in a process called opsonization. These proteins prime the particle for removal by immune cells and may contribute toward infusion-related adverse effects such as allergic responses. The ways complement proteins assemble on nanoparticles have remained unclear. Here, we show that dextran-coated superparamagnetic iron oxide core-shell nanoworms incubated in human serum and plasma are rapidly opsonized with the third complement component (C3) via the alternative pathway. Serum and plasma proteins bound to the nanoworms are mostly intercalated into the nanoworm shell. We show that C3 covalently binds to these absorbed proteins rather than the dextran shell and the protein-bound C3 undergoes dynamic exchange in vitro. Surface-bound proteins accelerate the assembly of the complement components of the alternative pathway on the nanoworm surface. When nanoworms pre-coated with human plasma were injected into mice, C3 and other adsorbed proteins undergo rapid loss. Our results provide important insight into dynamics of protein adsorption and complement opsonization of nanomedicines.
authors.affiliation: Department of Gastrointestinal Surgery, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, Jilin 130033, China.|The Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 East Montview Boulevard, Aurora, Colorado 80045, USA.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Chen
authors.affiliation: The Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 East Montview Boulevard, Aurora, Colorado 80045, USA.
authors.forename: Guankui
authors.initials: G
authors.lastname: Wang
authors.affiliation: The Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 East Montview Boulevard, Aurora, Colorado 80045, USA.
authors.forename: James I
authors.initials: JI
authors.lastname: Griffin
authors.affiliation: The Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 East Montview Boulevard, Aurora, Colorado 80045, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Brenneman
authors.affiliation: Division of Rheumatology, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, 1775 Aurora Court, Aurora, Colorado 80045, USA.
authors.forename: Nirmal K
authors.initials: NK
authors.lastname: Banda
authors.affiliation: Division of Rheumatology, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, 1775 Aurora Court, Aurora, Colorado 80045, USA.
authors.forename: V Michael
authors.initials: VM
authors.lastname: Holers
authors.affiliation: Computational Chemistry and Biology Core Facility, the Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 E. Montview Boulevard, Aurora, Colorado 80045, USA.
authors.forename: Donald S
authors.identifier: 0000-0001-6735-6210
authors.initials: DS
authors.lastname: Backos
authors.affiliation: Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Department of Pharmacy, Faculty of Health and Medical Sciences, Universitetsparken 2, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: LinPing
authors.initials: L
authors.lastname: Wu
authors.affiliation: Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Department of Pharmacy, Faculty of Health and Medical Sciences, Universitetsparken 2, University of Copenhagen, DK-2100 Copenhagen, Denmark.|NanoScience Centre, University of Copenhagen, DK-2100 Copenhagen, Denmark.|School of Medicine, Pharmacy and Health, Durham University, Queen's Campus, Stockton-on-Tees TS17 6BH, UK.
authors.forename: Seyed Moein
authors.initials: SM
authors.lastname: Moghimi
authors.affiliation: The Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 East Montview Boulevard, Aurora, Colorado 80045, USA.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Simberg
mesh_terms: D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003176:Complement C3 / Q000737:chemistry* / Q000378:metabolism; D003170:Complement Pathway, Alternative; D003911:Dextrans / Q000737:chemistry*; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry*
chemical_list: D020099:Coated Materials, Biocompatible; D003176:Complement C3; D003911:Dextrans; D058185:Magnetite Nanoparticles