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      An Evaluation of Blood Compatibility of Silver Nanoparticles

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          Abstract

          Silver nanoparticles (AgNPs) have tremendous potentials in medical devices due to their excellent antimicrobial properties. Blood compatibility should be investigated for AgNPs due to the potential blood contact. However, so far, most studies are not systematic and have not provided insights into the mechanisms for blood compatibility of AgNPs. In this study, we have investigated the blood biological effects, including hemolysis, lymphocyte proliferation, platelet aggregation, coagulation and complement activation, of 20 nm AgNPs with two different surface coatings (polyvinyl pyrrolidone and citrate). Our results have revealed AgNPs could elicit hemolysis and severely impact the proliferation and viability of lymphocytes at all investigated concentrations (10, 20, 40 μg/mL). Nevertheless, AgNPs didn’t show any effect on platelet aggregation, coagulation process, or complement activation at up to ~40 μg/mL. Proteomic analysis on AgNPs plasma proteins corona has revealed that acidic and small molecular weight blood plasma proteins were preferentially adsorbed onto AgNPs, and these include some important proteins relevant to hemostasis, coagulation, platelet, complement activation and immune responses. The predicted biological effects of AgNPs by proteomic analysis are mostly consistent with our experimental data since there were few C3 components on AgNPs and more negative than positive factors involving platelet aggregation and thrombosis.

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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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            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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              Nanosilver: a nanoproduct in medical application.

              Nanotechnology is a most promising field for generating new applications in medicine. However, only few nanoproducts are currently in use for medical purposes. A most prominent nanoproduct is nanosilver. Nanosilver particles are generally smaller than 100nm and contain 20-15,000 silver atoms. At nanoscale, silver exhibits remarkably unusual physical, chemical and biological properties. Due to its strong antibacterial activity, nanosilver coatings are used on various textiles but as well as coatings on certain implants. Further, nanosilver is used for treatment of wounds and burns or as a contraceptive and marketed as a water disinfectant and room spray. Thus, use of nanosilver is becoming more and more widespread in medicine and related applications and due to increasing exposure toxicological and environmental issues need to be raised. In sharp contrast to the attention paid to new applications of nanosilver, few studies provide only scant insights into the interaction of nanosilver particle with the human body after entering via different portals. Biodistribution, organ accumulation, degradation, possible adverse effects and toxicity are only slowly recognized and this review is focusing on major questions associated with the increased medical use of nanosilver and related nanomaterials.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                05 May 2016
                2016
                : 6
                : 25518
                Affiliations
                [1 ]Key Laboratory of Standardization and Measurement for Nanotechnology of Chinese Academy of Sciences, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , Beijing 100190, P. R. China
                [2 ]Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety of Chinese Academy of Sciences, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , Beijing 100190, P. R. China
                [3 ]College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou, 730000, P. R. China
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                srep25518
                10.1038/srep25518
                4857076
                27145858
                06ce7019-66c0-40b9-a419-1f4d77e966ef
                Copyright © 2016, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 25 January 2016
                : 15 April 2016
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