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      Magnetic field-controlled gene expression in encapsulated cells

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          Abstract

          Cell and gene therapies have an enormous range of potential applications, but as for most other therapies, dosing is a critical issue, which makes regulated gene expression a prerequisite for advanced strategies. Several inducible expression systems have been established, which mainly rely on small molecules as inducers, such as hormones or antibiotics. The application of these inducers is difficult to control and the effects on gene regulation are slow. Here we describe a novel system for induction of gene expression in encapsulated cells. This involves the modification of cells to express potential therapeutic genes under the control of a heat inducible promoter and the co-encapsulation of these cells with magnetic nanoparticles. These nanoparticles produce heat when subjected to an alternating magnetic field; the elevated temperatures in the capsules then induce gene expression. In the present study we define the parameters of such systems and provide proof-of-principle using reporter gene constructs. The fine-tuned heating of nanoparticles in the magnetic field allows regulation of gene expression from the outside over a broad range and within short time. Such a system has great potential for advancement of cell and gene therapy approaches.

          Graphical abstract

          Cells containing a heat inducible promoter construct (a) are encapsulated with magnetic nanoparticles (b+c). An alternating magnetic field produces heat (d), which allows controlled gene expression in patients (e).

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          Most cited references48

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          Hyperthermia in combined treatment of cancer.

          Hyperthermia, the procedure of raising the temperature of tumour-loaded tissue to 40-43 degrees C, is applied as an adjunctive therapy with various established cancer treatments such as radiotherapy and chemotherapy. The potential to control power distributions in vivo has been significantly improved lately by the development of planning systems and other modelling tools. This increased understanding has led to the design of multiantenna applicators (including their transforming networks) and implementation of systems for monitoring of E-fields (eg, electro-optical sensors) and temperature (particularly, on-line magnetic resonance tomography). Several phase III trials comparing radiotherapy alone or with hyperthermia have shown a beneficial effect of hyperthermia (with existing standard equipment) in terms of local control (eg, recurrent breast cancer and malignant melanoma) and survival (eg, head and neck lymph-node metastases, glioblastoma, cervical carcinoma). Therefore, further development of existing technology and elucidation of molecular mechanisms are justified. In recent molecular and biological investigations there have been novel applications such as gene therapy or immunotherapy (vaccination) with temperature acting as an enhancer, to trigger or to switch mechanisms on and off. However, for every particular temperature-dependent interaction exploited for clinical purposes, sophisticated control of temperature, spatially as well as temporally, in deep body regions will further improve the potential.
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            Clinical applications of magnetic nanoparticles for hyperthermia.

            Magnetic fluids are increasingly used for clinical applications such as drug delivery, magnetic resonance imaging and magnetic fluid hyperthermia. The latter technique that has been developed as a cancer treatment for several decades comprises the injection of magnetic nanoparticles into tumors and their subsequent heating in an alternating magnetic field. Depending on the applied temperature and the duration of heating this treatment either results in direct tumor cell killing or makes the cells more susceptible to concomitant radio- or chemotherapy. Numerous groups are working in this field worldwide, but only one approach has been tested in clinical trials so far. Here, we summarize the clinical data gained in these studies on magnetic fluid induced hyperthermia.
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              SEMIPERMEABLE MICROCAPSULES.

              T. Chang (1964)
              Simple methods have been developed for encapsulating aqueous solutions of protein within polymer membranes. Stable microcapsules 1 to 100 micro in diameter, with semipermeable membranes, can be made by depositing polymer around emulsified aqueous droplets, either by interfacial coacervation or by interfacial polycondensation. Aqueous suspensions of enzyme-loaded microcapsules act well on small-molecular substrates both in vitro and in vivo.
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                Author and article information

                Journal
                J Control Release
                J Control Release
                Journal of Controlled Release
                Elsevier Science Publishers
                0168-3659
                1873-4995
                28 March 2012
                28 March 2012
                : 158
                : 3
                : 424-432
                Affiliations
                [a ]University of Applied Sciences, FH Campus Wien, Department for Applied Life Sciences, Helmut-Qualtinger-Gasse 2, A-1030 Vienna, Austria
                [b ]Department for Biomedical Sciences, University of Veterinary Medicine, Veterinärplatz 1, A-1210 Vienna, Austria
                [c ]Department for Pathobiology, Institute of Virology, University of Veterinary Medicine, Veterinärplatz 1, A-1210 Vienna, Austria
                [d ]University of Applied Sciences, FH Campus Wien, Department for Engineering, Favoritenstrasse 226, A-1100 Vienna, Austria
                [e ]Department for Pathobiology, Institute for Experimental Oncology, Klinikum Rechts der Isar, TU Munich, Ismaninger Strasse 22, 81675 Munich, Germany
                [f ]Christian Doppler Laboratory for Gene Therapeutic Vector Development, Institute of Virology, University of Veterinary Medicine, Veterinärplatz 1, A-1210 Vienna, Austria
                [g ]SG Austria, 20 Biopolis Way, Centros #05-518, 138668, Singapore
                Author notes
                [* ]Corresponding author at: University of Applied Sciences, FH Campus Wien, Department for Applied Life Sciences, Helmut-Qualtinger-Gasse 2, A-1030 Vienna, Austria. Tel.: + 43 1 606 68 77 3511. thomas.czerny@ 123456fh-campuswien.ac.at
                [1]

                These authors contributed equally to this work.

                [2]

                Present address: ACIB, Muthgasse 11, A-1190 Vienna, Austria.

                Article
                COREL6122
                10.1016/j.jconrel.2011.12.006
                3329627
                22197778
                5db06fe0-8ec2-489b-8cb3-9bae4a4d2c7f
                © 2012 Elsevier B.V.

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 6 October 2011
                : 7 December 2011
                Categories
                Article

                Animal science & Zoology
                magnetic nanoparticles,inducible gene expression,cell therapy,gene therapy,hyperthermia,cell encapsulation

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