title: Protein Corona Modulates Uptake and Toxicity of Nanoceria via Clathrin-Mediated Endocytosis.
abstract: Particles present in diesel exhaust have been proposed as a significant contributor to the development of acute and chronic lung diseases, including respiratory infection and allergic asthma. Nanoceria (CeO2 nanoparticles) are used to increase fuel efficiency in internal combustion engines, are present in exhaust fumes, and could affect cells of the airway. Components from the environment such as biologically derived proteins, carbohydrates, and lipids can form a dynamic layer, commonly referred to as the "protein corona" which alters cellular nanoparticle interactions and internalization. Using confocal reflectance microscopy, we quantified nanoceria uptake by lung-derived cells in the presence and absence of a serum-derived protein corona. Employing mass spectrometry, we identified components of the protein corona, and demonstrated that the interaction between transferrin in the protein corona and the transferrin receptor is involved in mediating the cellular entry of nanoceria via clathrin-mediated endocytosis. Furthermore, under these conditions nanoceria does not affect cell growth, viability, or metabolism, even at high concentration. Alternatively, despite the antioxidant capacity of nanoceria, in serum-free conditions these nanoparticles induce plasma membrane disruption and cause changes in cellular metabolism. Thus, our results identify a specific receptor-mediated mechanism for nanoceria entry, and provide significant insight into the potential for nanoparticle-dependent toxicity.
authors.affiliation: School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom;
authors.forename: Julie
authors.initials: J
authors.lastname: Mazzolini
authors.affiliation: School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom;
authors.forename: Ralf J M
authors.initials: RJ
authors.lastname: Weber
authors.affiliation: Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu City 30, Taiwan;
authors.forename: Hsueh-Shih
authors.initials: HS
authors.lastname: Chen
authors.affiliation: School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom;
authors.forename: Abdullah
authors.initials: A
authors.lastname: Khan
authors.affiliation: School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom;
authors.forename: Emily
authors.initials: E
authors.lastname: Guggenheim
authors.affiliation: Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; and.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Shaw
authors.affiliation: School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom;
authors.forename: James K
authors.initials: JK
authors.lastname: Chipman
authors.affiliation: School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom;
authors.forename: Mark R
authors.initials: MR
authors.lastname: Viant
authors.affiliation: Center for Advanced Microscopy and Nikon Imaging Center, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, Illinois 60611 Joshua.rappoport@northwestern.edu.
authors.forename: Joshua Z
authors.initials: JZ
authors.lastname: Rappoport
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002563:Cerium / Q000378:metabolism / Q000633:toxicity*; D002966:Clathrin / Q000378:metabolism*; D016895:Culture Media, Serum-Free; D004705:Endocytosis; D006801:Humans; D053768:Metal Nanoparticles / Q000633:toxicity*; D000066970:Protein Corona / Q000737:chemistry / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
chemical_list: D002966:Clathrin; D016895:Culture Media, Serum-Free; D000066970:Protein Corona; D011990:Receptors, Transferrin; D014168:Transferrin; D002563:Cerium; C030583:ceric oxide