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Physical characterization and in vivo organ distribution of coated iron oxide nanoparticles

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      Abstract

      Citrate-stabilized iron oxide magnetic nanoparticles (MNPs) were coated with one of carboxymethyl dextran (CM-dextran), polyethylene glycol-polyethylene imine (PEG-PEI), methoxy-PEG-phosphate+rutin, or dextran. They were characterized for size, zeta potential, hysteresis heating in an alternating magnetic field, dynamic magnetic susceptibility, and examined for their distribution in mouse organs following intravenous delivery. Except for PEG-PEI-coated nanoparticles, all coated nanoparticles had a negative zeta potential at physiological pH. Nanoparticle sizing by dynamic light scattering revealed an increased nanoparticle hydrodynamic diameter upon coating. Magnetic hysteresis heating changed little with coating; however, the larger particles demonstrated significant shifts of the peak of complex magnetic susceptibility to lower frequency. 48 hours following intravenous injection of nanoparticles, mice were sacrificed and tissues were collected to measure iron concentration. Iron deposition from nanoparticles possessing a negative surface potential was observed to have highest accumulation in livers and spleens. In contrast, iron deposition from positively charged PEG-PEI-coated nanoparticles was observed to have highest concentration in lungs. These preliminary results suggest a complex interplay between nanoparticle size and charge determines organ distribution of systemically-delivered iron oxide magnetic nanoparticles.

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      Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications.

      Superparamagnetic iron oxide nanoparticles (SPION) with appropriate surface chemistry have been widely used experimentally for numerous in vivo applications such as magnetic resonance imaging contrast enhancement, tissue repair, immunoassay, detoxification of biological fluids, hyperthermia, drug delivery and in cell separation, etc. All these biomedical and bioengineering applications require that these nanoparticles have high magnetization values and size smaller than 100 nm with overall narrow particle size distribution, so that the particles have uniform physical and chemical properties. In addition, these applications need special surface coating of the magnetic particles, which has to be not only non-toxic and biocompatible but also allow a targetable delivery with particle localization in a specific area. To this end, most work in this field has been done in improving the biocompatibility of the materials, but only a few scientific investigations and developments have been carried out in improving the quality of magnetic particles, their size distribution, their shape and surface in addition to characterizing them to get a protocol for the quality control of these particles. Nature of surface coatings and their subsequent geometric arrangement on the nanoparticles determine not only the overall size of the colloid but also play a significant role in biokinetics and biodistribution of nanoparticles in the body. The types of specific coating, or derivatization, for these nanoparticles depend on the end application and should be chosen by keeping a particular application in mind, whether it be aimed at inflammation response or anti-cancer agents. Magnetic nanoparticles can bind to drugs, proteins, enzymes, antibodies, or nucleotides and can be directed to an organ, tissue, or tumour using an external magnetic field or can be heated in alternating magnetic fields for use in hyperthermia. This review discusses the synthetic chemistry, fluid stabilization and surface modification of superparamagnetic iron oxide nanoparticles, as well as their use for above biomedical applications.
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        Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications.

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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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            Author and article information

            Affiliations
            [1 ]Johns Hopkins University School of Medicine, Department of Radiation Oncology and Molecular Radiation Sciences, 1550 Orleans Street, CRB II, Baltimore, MD 21231 USA
            [2 ]Micromod Partikeltechnologie GmbH, Friedrich-Barnewitz-St 4, D-18119 Rostock, Germany
            [3 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Johns Hopkins Bloomberg School of Public Health, , Department of Environmental Health Sciences, ; Baltimore, MD 21205 USA
            [4 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Department of Mechanical Engineering, Whiting School of Engineering, , Johns Hopkins University, ; Baltimore, 21218 USA USA
            [5 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Department of Oncology, Sidney Kimmel Comprehensive Cancer Centre, School of Medicine, , Johns Hopkins University, ; Baltimore, MD 21231 USA
            [6 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Department of Materials Science and Engineering, Whiting School of Engineering, , Johns Hopkins University, ; Baltimore, 21218 USA
            [7 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Institute for NanoBioTechnology, Whiting School of Engineering, , Johns Hopkins University, ; Baltimore, 21218 USA
            Contributors
            rivkov1@jhmi.edu
            Journal
            Sci Rep
            Sci Rep
            Scientific Reports
            Nature Publishing Group UK (London )
            2045-2322
            20 March 2018
            20 March 2018
            2018
            : 8
            29559734
            5861066
            23317
            10.1038/s41598-018-23317-2
            © The Author(s) 2018

            Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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