Article | Published:

Biofunctionalized magnetic-vortex microdiscs for targeted cancer-cell destruction

Nature Materials volume 9, pages 165171 (2010) | Download Citation

Subjects

  • An Erratum to this article was published on 13 January 2010

This article has been updated

Abstract

Nanomagnetic materials offer exciting avenues for probing cell mechanics and activating mechanosensitive ion channels, as well as for advancing cancer therapies. Most experimental works so far have used superparamagnetic materials. This report describes a first approach based on interfacing cells with lithographically defined microdiscs that possess a spin-vortex ground state. When an alternating magnetic field is applied the microdisc vortices shift, creating an oscillation, which transmits a mechanical force to the cell. Because reduced sensitivity of cancer cells toward apoptosis leads to inappropriate cell survival and malignant progression, selective induction of apoptosis is of great importance for the anticancer therapeutic strategies. We show that the spin-vortex-mediated stimulus creates two dramatic effects: compromised integrity of the cellular membrane, and initiation of programmed cell death. A low-frequency field of a few tens of hertz applied for only ten minutes was sufficient to achieve 90% cancer-cell destruction in vitro.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Change history

  • 13 January 2010

    In the version of this Article originally published, the following sentence in the caption of Fig. 5 should have been written as: “Images of negative control (b,c) and MD-mAb-functionalized cells subjected to 20 Hz–90 Oe a.c. fields for 10 min and TUNEL stained 4 h after the magnetic-field exposure (d,e)” This has been corrected in all versions of this Article.

References

  1. 1.

    , & The emergence of spin electronics in data storage. Nature Mater. 6, 813–823 (2007).

  2. 2.

    et al. Real-time magnetic resonance imaging and quantification of lipoprotein metabolism in vivo using nanocrystals. Nature Nanotech. 4, 193–201 (2009).

  3. 3.

    Cancer nanotechnology: Opportunities and challenges. Nature Rev. Cancer 5, 161–171 (2005).

  4. 4.

    , , & Applications of magnetic nanoparticles in biomedicine. J. Phys. D 36, R167–R175 (2003).

  5. 5.

    , , & Magnetic particle hyperthermia: Nanoparticle magnetism and materials development for cancer therapy. J. Phys. Condens. Matter. 18, S2919–S2923 (2006).

  6. 6.

    Remote control of cellular behaviour with magnetic nanoparticles. Nature Nanotech. 3, 139–148 (2008).

  7. 7.

    et al. Nanomagnetic actuation of receptor-mediated signal transduction. Nature Nanotech. 3, 36–40 (2007).

  8. 8.

    , & Mechanotransduction across the cell surface and through the cytoskeleton. Science 260, 1124–1127 (1993).

  9. 9.

    , & Nanoscaling laws of magnetic nanoparticles and their applicability in biomedical science. Acc. Chem. Res. 41, 179–186 (2008).

  10. 10.

    & Synergistically integrated nanoparticles as multimodal probes for nanobiotechnology. Acc. Chem. Res. 41, 1630–1635 (2008).

  11. 11.

    , , & Single-domain circular nanomagnets. Phys. Rev. Lett. 83, 1042–1045 (1999).

  12. 12.

    , , , & Magnetic vortex core observation in circular dots of permalloy. Science 289, 930–933 (2000).

  13. 13.

    et al. Direct observation of internal spin structure of magnetic vortex cores. Science 298, 577–580 (2002).

  14. 14.

    et al. Soliton-pair dynamics in patterned ferromagnetic ellipses. Nature Phys. 1, 172–176 (2005).

  15. 15.

    & Near-edge X-ray absorption fine-structure microscopy of organic and magnetic materials. Nature Mater. 8, 281–290 (2009).

  16. 16.

    et al. Effect of interdot magnetostatic interaction on magnetization reversal in circular dot arrays. Phys. Rev. B 65, 060402 (2002).

  17. 17.

    et al. Ferromagnetic microdisks as carriers for biomedical applications. J. Appl. Phys. 105, 07B306 (2009).

  18. 18.

    , & Magnetic-field-induced optical transmittance in colloidal suspensions. Phys. Rev. E 59, 5676–5692 (1999).

  19. 19.

    et al. Understanding biophysicochemical interactions at the nano-bio interface. Nature Mater. 8, 543–557 (2009).

  20. 20.

    , , , & GFAP-positive human glioma cell lines: No. 10, no. 11. Hum. Cell 3, 251–256 (1990).

  21. 21.

    , , , & Receptor for interleukin 13 is a marker and therapeutic target for human high-grade gliomas. Cancer Res. 5, 985–990 (1999).

  22. 22.

    , , , & In vivo overexpression of IL-13 receptor {alpha}2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice. J. Exp. Med. 194, 1743–1754 (2001).

  23. 23.

    et al. A high-performance nanobio photocatalyst for targeted brain cancer therapy. Nano Lett. 9, 3337–3342 (2009).

  24. 24.

    , & Indentation and adhesive probing of a cell membrane with AFM: Theoretical model and experiments. Biophys. J. 89, 3203–3213 (2005).

  25. 25.

    , & Analysis of force curves obtained on the live cell membrane using chemically modified AFM probes. Ultramicroscopy 100, 187–195 (2004).

  26. 26.

    , , & Force probing surfaces of living cells to molecular resolution. Nature Chem. Biol. 5, 383–391 (2009).

  27. 27.

    & Differential staining of apoptotic nuclei in living cells: Application to macronuclear elimination in tetrahymena. J. Histochem. Cytochem. 45, 675–684 (1997).

  28. 28.

    et al. Role of DNAS1L3 in Ca2+- and Mg2+-dependent cleavage of DNA into oligonucleosomal and high molecular mass fragments. Nucl. Acids Res. 27, 1999–2005 (1999).

  29. 29.

    & Calcium orchestrates apoptosis. Nature Cell Biol. 5, 1041–1043 (2003).

  30. 30.

    Calcium signaling. Cell 80, 259–268 (1995).

  31. 31.

    Mitochondria and calcium: From cell signalling to cell death. J. Phys. 529, 57–68 (2000).

  32. 32.

    et al. Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. Nature Cell Biol. 5, 1051–1061 (2003).

  33. 33.

    Mechanosensitive ion channels: Molecules of mechanotransduction. J. Cell Sci. 117, 2449–2460 (2004).

  34. 34.

    & Stretch-activated single ion channel currents in tissue-cultured embryonic chick skeletal muscle. Physiol. (London) 352, 685–701 (1984).

  35. 35.

    , & Mechanically induced mobilization in cultured endothelial cells is dependent on actin and phospholipase. Arterioscler. Thromb. Vasc. Biol. 14, 2000–2006 (1994).

  36. 36.

    , & Directional dependence of osteoblastic calcium response to mechanical stimuli. Biomech. Model Mechanobiol. 2, 73–82 (2003).

  37. 37.

    & Magnetic particle hyperthermia—biophysical limitations of a visionary tumour therapy. J. Magn. Magn. Mater. 311, 187–192 (2007).

  38. 38.

    , & Magnetic nanoparticles for cancer therapy. Current Nanosci. 4, 1–16 (2008).

  39. 39.

    & Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26, 3995–4021 (2005).

Download references

Acknowledgements

We thank D. Clapham, R. Hergt, J. Dobson and A. Datesman for valuable suggestions and critical reading of the manuscript. We also thank J. Pearson for help with developing the magnetic-field induction set-up, R. Divan for discussing the microfabrication strategies, and V. Bindokas for technical assistance in Ca imaging at the UC Biological Sciences Division Light Microscopy Core Facility. Work at Argonne and its Center for Nanoscale Materials and Electron Microscopy Center is supported by the US Department of Energy Office of Science, Basic Energy Sciences, under contract No DE-AC02-06CH11357. Work at the University of Chicago is supported by the National Cancer Institute (R01-CA122930), the National Institute of Neurological Disorders and Stroke (K08-NS046430), the Alliance for Cancer Gene Therapy Young Investigator Award and the American Cancer Society (RSG-07-276-01-MGO).

Author information

Affiliations

  1. Materials Sciences Division, Argonne National Laboratory, Argonne, Illinois 60439, USA

    • Dong-Hyun Kim
    • , Samuel D. Bader
    •  & Valentyn Novosad
  2. Center for Nanoscale Materials, Argonne National Laboratory, Argonne, Illinois 60439, USA

    • Elena A. Rozhkova
    • , Samuel D. Bader
    •  & Tijana Rajh
  3. The Brain Tumor Center, The University of Chicago Pritzker School of Medicine, Chicago, Illinois 60637, USA

    • Ilya V. Ulasov
    •  & Maciej S. Lesniak

Authors

  1. Search for Dong-Hyun Kim in:

  2. Search for Elena A. Rozhkova in:

  3. Search for Ilya V. Ulasov in:

  4. Search for Samuel D. Bader in:

  5. Search for Tijana Rajh in:

  6. Search for Maciej S. Lesniak in:

  7. Search for Valentyn Novosad in:

Contributions

V.N. and E.A.R. conceived the experimental idea. M.S.L. advanced the conceptual design for the glioma cell targeting. I.V.U. performed in vitro and cell cytotoxicity studies. D.-H.K. and V.N. fabricated the magnetic microdiscs and carried out the magnetic characterization and micromagnetic modelling. D.-H.K. and E.A.R. ran the biofunctionalization experiments. D.-H.K. carried out atomic force and optical microscopy characterizations. E.A.R. and I.V.U. designed and analysed the intracellular Ca imaging experiments. D.-H.K., E.A.R., I.V.U., T.R., S.D.B., M.S.L. and V.N. analysed the data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Elena A. Rozhkova or Valentyn Novosad.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    Supplementary Information

Videos

  1. 1.

    Supplementary Information

    Supplementary Movie

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nmat2591

Further reading