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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

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.

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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.

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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).

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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). https://doi.org/10.1038/nmat2591

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