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      Carbohydrate functionalization of silver nanoparticles modulates cytotoxicity and cellular uptake

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          Abstract

          Background

          Increasing use of silver nanoparticles (Ag-NPs) in various products is resulting in a greater likelihood of human exposure to these materials. Nevertheless, little is still known about the influence of carbohydrates on the toxicity and cellular uptake of nanoparticles.

          Methods

          Ag-NPs functionalized with three different monosaccharides and ethylene glycol were synthesized and characterised. Oxidative stress and toxicity was evaluated by protein carbonylation and MTT assay, respectively. Cellular uptake was evaluated by confocal microscopy and ICP-MS.

          Results

          Ag-NPs coated with galactose and mannose were considerably less toxic to neuronal-like cells and hepatocytes compared to particles functionalized by glucose, ethylene glycol or citrate. Toxicity correlated to oxidative stress but not to cellular uptake.

          Conclusions

          Carbohydrate coating on silver nanoparticles modulates both oxidative stress and cellular uptake, but mainly the first has an impact on toxicity. These findings provide new perspectives on modulating the bioactivity of Ag-NPs by using carbohydrates.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12951-014-0059-z) contains supplementary material, which is available to authorized users.

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          Most cited references30

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          Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors

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            Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes.

            We investigated the mechanism by which transferrin-coated gold nanoparticles (Au NP) of different sizes and shapes entered mammalian cells. We determined that transferrin-coated Au NP entered the cells via clathrin-mediated endocytosis pathway. The NPs exocytosed out of the cells in a linear relationship to size. This was different than the relationship between uptake and size. Furthermore, we developed a mathematical equation to predict the relationship of size versus exocytosis for different cell lines. These studies will provide guidelines for developing NPs for imaging and drug delivery applications, which will require "controlling" NP accumulation rate. These studies will also have implications in determining nanotoxicity.
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              Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles.

              It is now clearly emerging that besides size and shape, the other primary defining element of nanoscale objects in biological media is their long-lived protein ("hard") corona. This corona may be expressed as a durable, stabilizing coating of the bare surface of nanoparticle (NP) monomers, or it may be reflected in different subpopulations of particle assemblies, each presenting a durable protein coating. Using the approach and concepts of physical chemistry, we relate studies on the composition of the protein corona at different plasma concentrations with structural data on the complexes both in situ and free from excess plasma. This enables a high degree of confidence in the meaning of the hard protein corona in a biological context. Here, we present the protein adsorption for two compositionally different NPs, namely sulfonated polystyrene and silica NPs. NP-protein complexes are characterized by differential centrifugal sedimentation, dynamic light scattering, and zeta-potential both in situ and once isolated from plasma as a function of the protein/NP surface area ratio. We then introduce a semiquantitative determination of their hard corona composition using one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray liquid chromatography mass spectrometry, which allows us to follow the total binding isotherms for the particles, identifying simultaneously the nature and amount of the most relevant proteins as a function of the plasma concentration. We find that the hard corona can evolve quite significantly as one passes from protein concentrations appropriate to in vitro cell studies to those present in in vivo studies, which has deep implications for in vitro-in vivo extrapolations and will require some consideration in the future.
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                Author and article information

                Contributors
                David.Kennedy@nrc-cnrc.gc.ca
                guillermo.orts-gil@mpikg.mpg.de
                Chian-Hui.Lai@mpikg.mpg.de
                larissa.mueller@bam.de
                Andrea.Haase@bfr.bund.de
                Andreas.Luch@bfr.bund.de
                Peter.Seeberger@mpikg.mpg.de
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                19 December 2014
                19 December 2014
                2014
                : 12
                : 1
                : 59
                Affiliations
                [ ]Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces (MPIKG), 14476 Potsdam, Germany
                [ ]Division 1.1 Inorganic Trace Analysis, Federal Institute for Materials Research and Testing (BAM), Richard-Willstätter-Straße 11, 12489 Berlin, Germany
                [ ]Departments Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), 10589 Berlin, Germany
                [ ]Institute for Chemistry and Biochemistry, Free University Berlin, Arnimallee 22, 14195 Berlin, Germany
                [ ]National Research Council Canada (CNRC), 100 Sussex Drive, Ottawa, Ontario Canada
                Article
                59
                10.1186/s12951-014-0059-z
                4275941
                25524171
                f54af31a-303c-41e1-9fb5-cfee6f3b44f1
                © Kennedy et al.; licensee BioMed Central. 2014

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 6 August 2014
                : 11 December 2014
                Categories
                Research
                Custom metadata
                © The Author(s) 2014

                Biotechnology
                silver,nanoparticles,carbohydrates,nanotoxicology,bio-interfaces
                Biotechnology
                silver, nanoparticles, carbohydrates, nanotoxicology, bio-interfaces

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