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      Proteomics Analysis Reveals Distinct Corona Composition on Magnetic Nanoparticles with Different Surface Coatings: Implications for Interactions with Primary Human Macrophages

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          Abstract

          Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as promising contrast agents for magnetic resonance imaging. The influence of different surface coatings on the biocompatibility of SPIONs has been addressed, but the potential impact of the so-called corona of adsorbed proteins on the surface of SPIONs on their biological behavior is less well studied. Here, we determined the composition of the plasma protein corona on silica-coated versus dextran-coated SPIONs using mass spectrometry-based proteomics approaches. Notably, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed distinct protein corona compositions for the two different SPIONs. Relaxivity of silica-coated SPIONs was modulated by the presence of a protein corona. Moreover, the viability of primary human monocyte-derived macrophages was influenced by the protein corona on silica-coated, but not dextran-coated SPIONs, and the protein corona promoted cellular uptake of silica-coated SPIONs, but did not affect internalization of dextran-coated SPIONs.

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          Most cited references26

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          The Proteomics Identifications (PRIDE) database and associated tools: status in 2013

          The PRoteomics IDEntifications (PRIDE, http://www.ebi.ac.uk/pride) database at the European Bioinformatics Institute is one of the most prominent data repositories of mass spectrometry (MS)-based proteomics data. Here, we summarize recent developments in the PRIDE database and related tools. First, we provide up-to-date statistics in data content, splitting the figures by groups of organisms and species, including peptide and protein identifications, and post-translational modifications. We then describe the tools that are part of the PRIDE submission pipeline, especially the recently developed PRIDE Converter 2 (new submission tool) and PRIDE Inspector (visualization and analysis tool). We also give an update about the integration of PRIDE with other MS proteomics resources in the context of the ProteomeXchange consortium. Finally, we briefly review the quality control efforts that are ongoing at present and outline our future plans.
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            Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts.

            Nanoparticles in a biological fluid (plasma, or otherwise) associate with a range of biopolymers, especially proteins, organized into the "protein corona" that is associated with the nanoparticle and continuously exchanging with the proteins in the environment. Methodologies to determine the corona and to understand its dependence on nanomaterial properties are likely to become important in bionanoscience. Here, we study the long-lived ("hard") protein corona formed from human plasma for a range of nanoparticles that differ in surface properties and size. Six different polystyrene nanoparticles were studied: three different surface chemistries (plain PS, carboxyl-modified, and amine-modified) and two sizes of each (50 and 100 nm), enabling us to perform systematic studies of the effect of surface properties and size on the detailed protein coronas. Proteins in the corona that are conserved and unique across the nanoparticle types were identified and classified according to the protein functional properties. Remarkably, both size and surface properties were found to play a very significant role in determining the nanoparticle coronas on the different particles of identical materials. We comment on the future need for scientific understanding, characterization, and possibly some additional emphasis on standards for the surfaces of nanoparticles.
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              Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy.

              At present, nanoparticles are used for various biomedical applications where they facilitate laboratory diagnostics and therapeutics. More specifically for drug delivery purposes, the use of nanoparticles is attracting increasing attention due to their unique capabilities and their negligible side effects not only in cancer therapy but also in the treatment of other ailments. Among all types of nanoparticles, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) with proper surface architecture and conjugated targeting ligands/proteins have attracted a great deal of attention for drug delivery applications. This review covers recent advances in the development of SPIONs together with their possibilities and limitations from fabrication to application in drug delivery. In addition, the state-of-the-art synthetic routes and surface modification of desired SPIONs for drug delivery purposes are described. Copyright © 2010 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 October 2015
                2015
                : 10
                : 10
                : e0129008
                Affiliations
                [1 ]Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
                [2 ]Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Science for Life Laboratory, and Karolinska Institutet, Stockholm, Sweden
                [3 ]NMR and Molecular Imaging Laboratory, Department of General, Organic and Biomedical Chemistry, University of Mons, Mons, Belgium
                [4 ]Electron Microscopy Core Facility, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
                [5 ]Division of Metals & Health, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
                [6 ]Functional Materials Division, School of Information and Communication Technology, Royal Institute of Technology, Stockholm, Sweden
                RMIT University, AUSTRALIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: BF MT. Performed the experiments: CV MP KH SL. Analyzed the data: CV PK BF MV JL MT. Contributed reagents/materials/analysis tools: CV PK MP MV JL BF MT. Wrote the paper: CV BF.

                [¤]

                Current address: Department of Applied Physics, Royal Institute of Technology, Stockholm, Sweden

                Article
                PONE-D-14-50625
                10.1371/journal.pone.0129008
                4596693
                26444829
                0865b603-bd01-4b31-8841-86d0f1b74731
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 16 November 2014
                : 4 May 2015
                Page count
                Figures: 5, Tables: 4, Pages: 20
                Funding
                This work was supported by Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (BF), the Swedish Cancer and Allergy Foundation (BF), the Swedish Cancer Society (JL), the Swedish Research Council (BF, JL), and the European Commission (FP7-NANOSOLUTIONS, grant agreement no. 309329) (BF) and FP7-eNANOMAPPER, grant agreement no. 604134) (BF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files. Additionally, all proteomics data generated in this study are deposited to the ProteomeXchange Consortium ( http://proteomecentral.proteomexchange.org) with the dataset identifier PXD000766.

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