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Identification of Magnetic Nanoparticles for Combined Positioning and Lentiviral Transduction of Endothelial Cells

  • Research Paper Theme: Magnetic Nano
  • Published:
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Abstract

Purpose

The combination of magnetic nanoparticles (MNPs) with a magnetic field is a powerful approach to enable cell positioning and/or local gene therapy. Because physical requirements for MNPs differ between these two applications we have explored whether the use of different MNPs can provide site-specific positioning combined with efficient viral transduction of endothelial cells (ECs).

Methods

A variety of MNPs was screened for magnetic cell labeling and lentivirus binding. Then two different MNPs were chosen and their combined application was evaluated regarding EC magnetization and transduction efficiency.

Results

The combined use of PEI-Mag2 and NDT-Mag1 particles provided both efficient lentiviral transduction and high magnetic responsiveness of ECs that could be even retained within the vascular wall under flow conditions. The use of these MNPs did not affect biological characteristics of ECs like surface marker expression and vascular network formation. Importantly, with this method we could achieve an efficient functional overexpression of endothelial nitric oxide synthase in ECs.

Conclusions

The application of two different MNPs provides optimal results for magnetic labeling of ECs in combination with viral transduction. This novel approach could be very useful for targeted gene therapy ex vivo and site-specific cell replacement in the vascular system.

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Abbreviations

bPAECs:

bovine pulmonary endothelial cells

CMV:

cytomegalovirus

ECs:

endothelial cells

eGFP:

enhanced green fluorescent protein

eNOS:

endothelial nitric oxide synthase

Fe:

iron

LV:

lentivirus

MNPs:

magnetic nanoparticles

MOI:

multiplicity of infection

MPS:

magnetic particle spectroscopy

NDT/PEI (0.04):

NDT-Mag1/PEI-Mag2 at a ratio of 0.04 pg Fe/VP

NDT/PEI (25):

NDT-Mag1/PEI-Mag2 at a ratio of 25 pg Fe/cell

PECAM:

platelet endothelial cell adhesion molecule

VP:

virus particle

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Acknowledgments & Disclosures

We thank Dr. Peter Newman (University of Wisconsin) for providing a PECAM antibody and Dr. Christian Plank for helpful discussion. Funding was provided to the junior research group “Magnetic nanoparticles (MNPs)—endothelial cell replacement in injured vessels” by the Ministry of Innovation, Science, Research and Technology of the State of North Rhine-Westphalia (DW) and the DFG Research Unit FOR 917 Nanoguide (AP, CP, BKF, LT).

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Authors and Affiliations

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

    Daniela Wenzel, Sarah Rieck, Sarah Vosen & Bernd K. Fleischmann

  2. Institute of Experimental Oncology, TU München, Munich, Germany

    Olga Mykhaylyk

  3. Institute of Pharmacology and Toxicology, University of Bonn, Bonn, Germany

    Christina Trueck, Katrin Zimmermann & Alexander Pfeifer

  4. Physikalisch-Technische Bundesanstalt, Berlin, Germany

    Dietmar Eberbeck & Lutz Trahms

Authors
  1. Daniela Wenzel
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  2. Sarah Rieck
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  3. Sarah Vosen
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  4. Olga Mykhaylyk
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  5. Christina Trueck
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  6. Dietmar Eberbeck
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  7. Lutz Trahms
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  8. Katrin Zimmermann
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  9. Alexander Pfeifer
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  10. Bernd K. Fleischmann
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Corresponding author

Correspondence to Daniela Wenzel.

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Wenzel, D., Rieck, S., Vosen, S. et al. Identification of Magnetic Nanoparticles for Combined Positioning and Lentiviral Transduction of Endothelial Cells. Pharm Res 29, 1242–1254 (2012). https://doi.org/10.1007/s11095-011-0657-5

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  • DOI: https://doi.org/10.1007/s11095-011-0657-5

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