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      Magnetocontrollability of Fe 7C 3@C superparamagnetic nanoparticles in living cells

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          Abstract

          Background

          A new type of superparamagnetic nanoparticles with chemical formula Fe7C3@C (MNPs) showed higher value of magnetization compared to traditionally used iron oxide-based nanoparticles as was shown in our previous studies. The in vitro biocompatibility tests demonstrated that the MNPs display high efficiency of cellular uptake and do not affect cyto-physiological parameters of cultured cells. These MNPs display effective magnetocontrollability in homogeneous liquids but their behavior in cytoplasm of living cells under the effect of magnetic field was not carefully analyzed yet.

          Results

          In this work we investigated the magnetocontrollability of MNPs interacting with living cells in permanent magnetic field. It has been shown that cells were capable of capturing MNPs by upper part of the cell membrane, and from the surface of the cultivation substrate during motion process. Immunofluorescence studies using intracellular endosomal membrane marker showed that MNP agglomerates can be either located in endosomes or lying free in the cytoplasm. When attached cells were exposed to a magnetic field up to 0.15 T, the MNPs acquired magnetic moment and the displacement of incorporated MNP agglomerates in the direction of the magnet was observed. Weakly attached or non-attached cells, such as cells in mitosis or after cytoskeleton damaging treatments moved towards the magnet. During long time cultivation of cells with MNPs in a magnetic field gradual clearing of cells from MNPs was observed. It was the result of removing MNPs from the surface of the cell agglomerates discarded in the process of exocytosis.

          Conclusions

          Our data allow us to conclude for the first time that the magnetic properties of the MNPs are sufficient for successful manipulation with MNP agglomerates both at the intracellular level, and within the whole cell. The structure of the outer shells of the MNPs allows firmly associate different types of biological molecules with them. This creates prospects for the use of such complexes for targeted delivery and selective removal of selected biological molecules from living cells.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12951-016-0219-4) contains supplementary material, which is available to authorized users.

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          Most cited references27

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          Endosomal escape pathways for delivery of biologicals.

          Despite continuous improvements in delivery systems, the development of methods for efficient and specific delivery of targeted therapeutic agents still remains an issue in biological treatments such as protein and gene therapy. The endocytic pathway is the major uptake mechanism of cells and any biological agents, such as DNA, siRNA and proteins. These agents become entrapped in endosomes and are degraded by specific enzymes in the lysosome. Thus, a limiting step in achieving an effective biological based therapy is to facilitate the endosomal escape and ensure cytosolic delivery of the therapeutics. Bacteria and viruses are pathogens which use different mechanisms to penetrate the membranes of their target cells and escape the endosomal pathway. Different mechanisms such as pore formation in the endosomal membrane, pH-buffering effect of protonable groups and fusion into the lipid bilayer of endosomes have been proposed to facilitate the endosomal escape. Several viral and bacterial proteins have been identified that are involved in this process. In addition, chemical agents and photochemical methods to rupture the endosomal membrane have been described. New synthetic biomimetic peptides and polymers with high efficacy in facilitating the endosomal escape, low pathogenicity and toxicity have been developed. Each strategy has different characteristics and challenges for designing the best agents and techniques to facilitate the endosomal escape are ongoing. In this review, several mechanisms and agents which are involved in endosomal escape are introduced. Copyright © 2010 Elsevier B.V. All rights reserved.
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            Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo.

            Low efficiencies of nonviral gene vectors, the receptor-dependent host tropism of adenoviral or low titers of retroviral vectors limit their utility in gene therapy. To overcome these deficiencies, we associated gene vectors with superparamagnetic nanoparticles and targeted gene delivery by application of a magnetic field. This potentiated the efficacy of any vector up to several hundred-fold, allowed reduction of the duration of gene delivery to minutes, extended the host tropism of adenoviral vectors to nonpermissive cells and compensated for low retroviral titer. More importantly, the high transduction efficiency observed in vitro was reproduced in vivo with magnetic field-guided local transfection in the gastrointestinal tract and in blood vessels. Magnetofection provides a novel tool for high throughput gene screening in vitro and can help to overcome fundamental limitations to gene therapy in vivo.
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              Phagosome maturation: going through the acid test.

              Phagosome maturation is the process by which internalized particles (such as bacteria and apoptotic cells) are trafficked into a series of increasingly acidified membrane-bound structures, leading to particle degradation. The characterization of the phagosomal proteome and studies in model organisms and mammals have led to the identification of numerous candidate proteins that cooperate to control the maturation of phagosomes containing different particles. A subset of these candidate proteins makes up the first pathway to be identified for the maturation of apoptotic cell-containing phagosomes. This suggests that a machinery that is distinct from receptor-mediated endocytosis is used in phagosome maturation.
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                Author and article information

                Contributors
                irina_alieva@mail.ru
                kireev@genebee.msu.ru
                anastasiacit@gmail.com
                alyabyeva@univ-tours.fr
                antoine.ruyter@univ-tours.fr
                olgastrelkova@gmail.com
                oxana.zhironkina@gmail.com
                vvvvvdddd@gmail.com
                alexander.majouga@gmail.com
                vdavydov@hppi.troitsk.ru
                Valery.Khabashesku@bakerhughes.com
                viatcheslav.agafonov@univ-tours.fr
                rustem.uzbekov@univ-tours.fr
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                30 August 2016
                30 August 2016
                2016
                : 14
                : 1
                : 67
                Affiliations
                [1 ]A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia 119992
                [2 ]Biology Faculty, Moscow State University, Moscow, Russia 119992
                [3 ]GREMAN, UMR CNRS 7347, Université François Rabelais, 37200 Tours, France
                [4 ]Chemistry Faculty, Moscow State University, Moscow, Russia 119992
                [5 ]MISiS, Leninskiy prospekt 2, Moscow, Russia 119049
                [6 ]Institute of High Pressure Physics RAS, Troitsk, Moscow region Russia 142190
                [7 ]Center for Technology Innovation, Baker Hughes Inc., Houston, TX 77040 USA
                [8 ]Laboratoire Biologie Cellulaire et Microscopie Electronique, Faculté de Médecine, Université François Rabelais, 37032 Tours, France
                [9 ]Faculty of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia 119992
                Author information
                http://orcid.org/0000-0002-9336-5484
                Article
                219
                10.1186/s12951-016-0219-4
                5006615
                27576904
                c38efde8-0806-4ec1-b1f0-392d1252ea08
                © The Author(s) 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 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
                : 27 April 2016
                : 18 August 2016
                Funding
                Funded by: Russian Foundation for Basic Research (RU)
                Award ID: 15-03-04490
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100002261, Russian Foundation for Basic Research;
                Award ID: 15-04-08550
                Award ID: 15-54-77078
                Award Recipient :
                Funded by: Lomonosov Moscow State University Development Program
                Award ID: PNR 5.13
                Award Recipient :
                Funded by: The NUST MISiS grant designed to invite Leading scientists for short term joined research projects
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Biotechnology
                superparamagnetic nanoparticles,living cells,magnetocontrollability,endocytosis,cytoskeleton,cell adhesion

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