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Local Gene Targeting and Cell Positioning Using Magnetic Nanoparticles and Magnetic Tips: Comparison of Mathematical Simulations with Experiments

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ABSTRACT

Purpose

Magnetic nanoparticles (MNPs) and magnets can be used to enhance gene transfer or cell attachment but gene or cell delivery to confined areas has not been addressed. We therefore searched for an optimal method to simulate and perform local gene targeting and cell delivery in vitro.

Methods

Localized gene transfer or cell positioning was achieved using permanent magnets with newly designed soft iron tips and MNP/lentivirus complexes or MNP-loaded cells, respectively. Their distribution was simulated with a mathematical model calculating magnetic flux density gradients and particle trajectories.

Results

Soft iron tips generated strong confined magnetic fields and could be reliably used for local (~500 μm diameter) gene targeting and positioning of bone marrow cells or cardiomyocytes. The calculated distribution of MNP/lentivirus complexes and MNP-loaded cells concurred very well with the experimental results of local gene expression and cell attachment, respectively.

Conclusion

MNP-based gene targeting and cell positioning can be reliably performed in vitro using magnetic soft iron tips, and computer simulations are effective methods to predict and optimize experimental results.

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Abbreviations

BMC:

bone marrow cells

GFP:

green fluorescent protein

MNP:

magnetic nanoparticle

MEA:

microelectrode array

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ACKNOWLEDGMENTS & DISCLOSURES

We thank O. Mykhaylyk and C. Plank, Institute for Experimental Oncology and Therapy Research, Technische Universitaet Muenchen, Germany for providing the SO-Mag5 MNP, K. Zimmermann and A. Pfeifer, Institute of Pharmacology and Toxicology, University of Bonn, Germany for providing the cytomegalovirus-GFP lentivirus, W. C. Claycomb, New Orleans, USA for providing the HL-1 cell line, and K. Granitza and the machine shop of the Institute of Physiology, University Bonn for machining the soft iron tips.

This work was supported by grants of the German Research Foundation within the DFG Research Unit 917 “Nanoparticle-based targeting of gene- and cell-based therapies.”

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Authors and Affiliations

  1. Institute of Physiology I, Life and Brain Center, University of Bonn, Sigmund-Freud-Str.25, 53127, Bonn, Germany

    Carsten Kilgus, Annika Ottersbach, Bernd K. Fleischmann & Philipp Sasse

  2. Zentralinstitut für Medizintechnik, Technische Universität München, Boltzmannstr. 11, 85748, Garching, Germany

    Alexandra Heidsieck & Bernhard Gleich

  3. Department of Cardiac Surgery, University of Bonn, Bonn, Germany

    Wilhelm Roell

  4. Institute of Pharmacology and Toxicology, Biomedical Center, University of Bonn, Bonn, Germany

    Christina Trueck

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  1. Carsten Kilgus
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  2. Alexandra Heidsieck
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  4. Wilhelm Roell
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Corresponding authors

Correspondence to Bernhard Gleich or Philipp Sasse.

Additional information

Carsten Kilgus and Alexandra Heidsieck contributed equally to this manuscript.

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Kilgus, C., Heidsieck, A., Ottersbach, A. et al. Local Gene Targeting and Cell Positioning Using Magnetic Nanoparticles and Magnetic Tips: Comparison of Mathematical Simulations with Experiments. Pharm Res 29, 1380–1391 (2012). https://doi.org/10.1007/s11095-011-0647-7

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  • DOI: https://doi.org/10.1007/s11095-011-0647-7

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