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      In vivo degeneration and the fate of inorganic nanoparticles.

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          Abstract

          What happens to inorganic nanoparticles (NPs), such as plasmonic gold or silver, superparamagnetic iron oxide, or fluorescent quantum dot NPs after they have been administrated to a living being? This review discusses the integrity, biodistribution, and fate of NPs after in vivo administration. The hybrid nature of the NPs is described, conceptually divided into the inorganic core, the engineered surface coating comprising of the ligand shell and optionally also bio-conjugates, and the corona of adsorbed biological molecules. Empirical evidence shows that all of these three compounds may degrade individually in vivo and can drastically modify the life cycle and biodistribution of the whole heterostructure. Thus, the NPs may be decomposed into different parts, whose biodistribution and fate would need to be analyzed individually. Multiple labeling and quantification strategies for such a purpose will be discussed. All reviewed data indicate that NPs in vivo should no longer be considered as homogeneous entities, but should be seen as inorganic/organic/biological nano-hybrids with complex and intricately linked distribution and degradation pathways.

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          Most cited references148

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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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            Strength and Breaking Mechanism of Multiwalled Carbon Nanotubes Under Tensile Load

            M Yu (2000)
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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

                Journal
                Chem Soc Rev
                Chemical Society reviews
                Royal Society of Chemistry (RSC)
                1460-4744
                0306-0012
                May 03 2016
                : 45
                : 9
                Affiliations
                [1 ] Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat, Karolinska Institutet, Stockholm, Sweden and Fachbereich Physik, Philipps Universität Marburg, Marburg, Germany. wolfgang.parak@physik.uni-marburg.de.
                [2 ] Department of Nanobiomedicine, ENT/University Medical Center of Mainz, Mainz, Germany. roland.stauber@unimedizin-mainz.de.
                [3 ] Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. nielsen@uke.uni-hamburg.de.
                [4 ] Fachbereich Physik, Philipps Universität Marburg, Marburg, Germany. wolfgang.parak@physik.uni-marburg.de and Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS) and Departamento de Física de la Materia Condensada, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain and CIC biomaGUNE, 20009 Donostia-San Sebastián, Spain.
                [5 ] Fachbereich Physik, Philipps Universität Marburg, Marburg, Germany. wolfgang.parak@physik.uni-marburg.de.
                [6 ] Laboratoire Matière et Systèmes Complexes, UMR 7057 CNRS/Université Paris Diderot, Paris, France. florence.gazeau@univ-paris-diderot.fr.
                [7 ] Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Ear, Nose and Throat, Karolinska Institutet, Stockholm, Sweden.
                [8 ] Laboratoire Matériaux et Phénomènes Quantiques, UMR 7162 CNRS/Université Paris Diderot, Paris, France. damien.alloyeau@univ-paris-diderot.fr.
                [9 ] Fachbereich Physik, Philipps Universität Marburg, Marburg, Germany. wolfgang.parak@physik.uni-marburg.de and CIC biomaGUNE, 20009 Donostia-San Sebastián, Spain.
                Article
                10.1039/c5cs00699f
                26862602
                79d068e4-0b8a-4297-8d90-a11c8b44df2f
                History

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