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A magnetic switch for the control of cell death signalling in in vitro and in vivo systems

Nature Materials volume 11, pages 1038–1043 (2012)Cite this article

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Abstract

The regulation of cellular activities in a controlled manner is one of the most challenging issues in fields ranging from cell biology to biomedicine1,2. Nanoparticles have the potential of becoming useful tools for controlling cell signalling pathways in a space and time selective fashion3,4. Here, we have developed magnetic nanoparticles that turn on apoptosis cell signalling by using a magnetic field in a remote and non-invasive manner. The magnetic switch consists of zinc-doped iron oxide magnetic nanoparticles5 (Zn0.4Fe2.6O4), conjugated with a targeting antibody for death receptor 4 (DR4) of DLD-1 colon cancer cells. The magnetic switch, in its On mode when a magnetic field is applied to aggregate magnetic nanoparticle-bound DR4s, promotes apoptosis signalling pathways. We have also demonstrated that the magnetic switch is operable at the micrometre scale and that it can be applied in an in vivo system where apoptotic morphological changes of zebrafish are successfully induced.

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Figure 1: A schematic representation of the magnetic switch for apoptosis signalling in in vitro cells and in a zebrafish.
Figure 2: Antibody-conjugated MNPs and the magnetic switch set-up for apoptosis signalling.
Figure 3: In vitro apoptosis induction in the DLD-1 colon cancer cell line.
Figure 4: Spatial control of apoptosis signalling.
Figure 5: In vivo magnetic apoptosis signalling for zebrafish.

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Acknowledgements

This work was financially supported by grants from the Creative Research Initiative (2010-0018286), WCU Program (R32-10217), National Research Foundation of Korea (2011-0017611) and the second stage BK21 for Chemistry and Medical Sciences of Yonsei University. S.W.P. was supported by the National Research Foundation, Mid-career Researcher Program (72011-0043). M.H.C. was supported by a Hi Seoul Science/Humanities Fellowship from the Seoul Scholarship Foundation.

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  1. Mi Hyeon Cho, Eun Jung Lee and Mina Son: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Chemistry, Yonsei University, Seoul 120-749, Korea

    Mi Hyeon Cho, Eun Jung Lee, Jae-Hyun Lee, Dongwon Yoo, Ji-wook Kim & Jinwoo Cheon

  2. Graduate Program for Nanomedical Science, Yonsei University, Seoul 120-749, Korea

    Eun Jung Lee, Mina Son, Jeon-Soo Shin & Jinwoo Cheon

  3. Department of Internal Medicine, Institute of Gastroenterology, College of Medicine, Yonsei University, Seoul 120-752, Korea

    Seung Woo Park

  4. Department of Microbiology, Severance Biomedical Science Institute, Institute for Immunology and Immunological Diseases, College of Medicine, Yonsei University, Seoul 120-752, Korea

    Jeon-Soo Shin

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  1. Mi Hyeon Cho
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Contributions

J.C. and J-S.S. conceived and designed the experiments. M.H.C., E.J.L., M.S. and J-w.K. performed the experiments. S.W.P. provided advice on the in vivo zebrafish experiments. M.H.C., E.J.L., J-H.L., D.Y., J-S.S. and J.C. wrote the manuscript.

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Correspondence to Jeon-Soo Shin or Jinwoo Cheon.

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Cho, M., Lee, E., Son, M. et al. A magnetic switch for the control of cell death signalling in in vitro and in vivo systems. Nature Mater 11, 1038–1043 (2012). https://doi.org/10.1038/nmat3430

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