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Biofunctionalized magnetic-vortex microdiscs for targeted cancer-cell destruction

An Erratum to this article was published on 13 January 2010

This article has been updated


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.

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Figure 1: The concept of targeted magnetomechanical cancer-cell destruction using disc-shaped magnetic particles possessing a spin-vortex ground state.
Figure 2: Magnetic-vortex microdiscs can be distantly actuated by the application of small-amplitude and low-frequency a.c. magnetic fields.
Figure 3: A low-frequency spatially uniform magnetic field applied to the MDs–mAb–cell complex results in compromised integrity of the cellular membrane and cell death.
Figure 4: Comparison of representative atomic force microscope amplitude error, height and cross-section scans for the control and treated cells.
Figure 5: Magnetic-vortex-mediated mechanical stimuli trigger intracellular biochemical pathways activating programmed cell death.
Figure 6: Optical imaging of intracellular calcium.

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.


  1. 1

    Chappert, C., Fert, A. & Van Dau, F. N. The emergence of spin electronics in data storage. Nature Mater. 6, 813–823 (2007).

    CAS  Article  Google Scholar 

  2. 2

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

    CAS  Article  Google Scholar 

  3. 3

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

    CAS  Google Scholar 

  4. 4

    Pankhurst, Q. A., Connolly, J., Jones, S. K. & Dobson, J. Applications of magnetic nanoparticles in biomedicine. J. Phys. D 36, R167–R175 (2003).

    CAS  Article  Google Scholar 

  5. 5

    Hergt, R., Dutz, S., Muller, R. & Zeisberger, M. Magnetic particle hyperthermia: Nanoparticle magnetism and materials development for cancer therapy. J. Phys. Condens. Matter. 18, S2919–S2923 (2006).

    CAS  Article  Google Scholar 

  6. 6

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

    CAS  Article  Google Scholar 

  7. 7

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

    Article  Google Scholar 

  8. 8

    Wang, N., Butler, J. P. & Ingber, D. E. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260, 1124–1127 (1993).

    CAS  Article  Google Scholar 

  9. 9

    Jun, Y.-W., Seo, J.-W. & Cheon, J. Nanoscaling laws of magnetic nanoparticles and their applicability in biomedical science. Acc. Chem. Res. 41, 179–186 (2008).

    CAS  Google Scholar 

  10. 10

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

    CAS  Article  Google Scholar 

  11. 11

    Cowburn, R. P., Koltsov, D. K., Adeyeye, A. O. & Welland, M. E. Single-domain circular nanomagnets. Phys. Rev. Lett. 83, 1042–1045 (1999).

    CAS  Article  Google Scholar 

  12. 12

    Shinjo, T., Okuno, T., Hassdorf, R., Shigeto, K. & Ono, T. Magnetic vortex core observation in circular dots of permalloy. Science 289, 930–933 (2000).

    CAS  Article  Google Scholar 

  13. 13

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

    CAS  Article  Google Scholar 

  14. 14

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

    CAS  Article  Google Scholar 

  15. 15

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

    CAS  Article  Google Scholar 

  16. 16

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

    Article  Google Scholar 

  17. 17

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

    Article  Google Scholar 

  18. 18

    Martin, J. E., Hill, K. M. & Tigges, C. P. Magnetic-field-induced optical transmittance in colloidal suspensions. Phys. Rev. E 59, 5676–5692 (1999).

    CAS  Article  Google Scholar 

  19. 19

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

    CAS  Article  Google Scholar 

  20. 20

    Da, K., Shiyama, K., Naka, R., Hiyama, A. & Anishi, T. GFAP-positive human glioma cell lines: No. 10, no. 11. Hum. Cell 3, 251–256 (1990).

    Google Scholar 

  21. 21

    Debinski, W., Gibo, D., Hulet, S., Connor, J. & Gillespie, G. Receptor for interleukin 13 is a marker and therapeutic target for human high-grade gliomas. Cancer Res. 5, 985–990 (1999).

    CAS  Google Scholar 

  22. 22

    Kawakami, K., Kawakami, M., Snoy, P. J., Husain, S. R. & Puri, R. K. 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).

    CAS  Article  Google Scholar 

  23. 23

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

    CAS  Article  Google Scholar 

  24. 24

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

    CAS  Article  Google Scholar 

  25. 25

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

    CAS  Article  Google Scholar 

  26. 26

    Muller, D., Helenius, J., Alsteens, D. & Dufrêne, Y. Force probing surfaces of living cells to molecular resolution. Nature Chem. Biol. 5, 383–391 (2009).

    Article  Google Scholar 

  27. 27

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

    CAS  Article  Google Scholar 

  28. 28

    Yakovlev, A. G. 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).

    CAS  Article  Google Scholar 

  29. 29

    Mattson, M. P. & Chan, S. L. Calcium orchestrates apoptosis. Nature Cell Biol. 5, 1041–1043 (2003).

    CAS  Article  Google Scholar 

  30. 30

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

    CAS  Article  Google Scholar 

  31. 31

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

    CAS  Google Scholar 

  32. 32

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

    CAS  Article  Google Scholar 

  33. 33

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

    CAS  Article  Google Scholar 

  34. 34

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

    CAS  Article  Google Scholar 

  35. 35

    Diamond, S. L., Sachs, F. & Sigurdson, W. J. Mechanically induced mobilization in cultured endothelial cells is dependent on actin and phospholipase. Arterioscler. Thromb. Vasc. Biol. 14, 2000–2006 (1994).

    CAS  Article  Google Scholar 

  36. 36

    Adachi, T., Sato, K. & Tomita, Y. Directional dependence of osteoblastic calcium response to mechanical stimuli. Biomech. Model Mechanobiol. 2, 73–82 (2003).

    CAS  Article  Google Scholar 

  37. 37

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

    CAS  Article  Google Scholar 

  38. 38

    Goya, G. F., Grazu, V. & Ibarra, M. R. Magnetic nanoparticles for cancer therapy. Current Nanosci. 4, 1–16 (2008).

    CAS  Article  Google Scholar 

  39. 39

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

    CAS  Article  Google Scholar 

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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).

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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.

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Correspondence to Elena A. Rozhkova or Valentyn Novosad.

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The authors declare no competing financial interests.

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Kim, DH., Rozhkova, E., Ulasov, I. et al. Biofunctionalized magnetic-vortex microdiscs for targeted cancer-cell destruction. Nature Mater 9, 165–171 (2010).

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