Full Paper

Inhibition of Tumor-Cell Invasion with Chlorotoxin-Bound Superparamagnetic Nanoparticles

  1. Omid Veiseh1,
  2. Jonathan W. Gunn1,
  3. Forrest M. Kievit1,
  4. Conroy Sun1,
  5. Chen Fang1,
  6. Jerry S. H. Lee2,3,
  7. Miqin Zhang1,*

Article first published online: 16 DEC 2008

DOI: 10.1002/smll.200800646

Issue

Small

Small

Volume 5, Issue 2, pages 256–264, January 19, 2009

Additional Information

How to Cite

Veiseh, O., Gunn, J. W., Kievit, F. M., Sun, C., Fang, C., Lee, J. S. H. and Zhang, M. (2009), Inhibition of Tumor-Cell Invasion with Chlorotoxin-Bound Superparamagnetic Nanoparticles. Small, 5: 256–264. doi: 10.1002/smll.200800646

Author Information

  1. 1

    Department of Materials Science and Engineering, University of Washington Seattle, WA 98195 (USA)

  2. 2

    Office of the Director National Cancer Institute, National Institutes of Health Bethesda, MD 20892 (USA)

  3. 3

    Department of Chemical and Biomolecular Engineering John Hopkins University Baltimore, MD 21218 (USA)

*Department of Materials Science and Engineering, University of Washington Seattle, WA 98195 (USA).

Publication History

  1. Issue published online: 19 JAN 2009
  2. Article first published online: 16 DEC 2008
  3. Manuscript Revised: 13 JUL 2008
  4. Manuscript Received: 6 MAY 2008

Funded by

  • NIH. Grant Numbers: NCI 5R01CA9408, NIBIB R01EB006043, NCI 5R01CA112350
  • NIH. Grant Number: T32GM065098

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Keywords:

  • antitumor agents;
  • biological materials;
  • cells;
  • imaging;
  • peptides

Abstract

Nanoparticles have been investigated as drug delivery vehicles, contrast agents, and multifunctional devices for patient care. Current nanoparticle-based therapeutic strategies for cancer treatment are mainly based on delivery of chemotherapeutic agents to induce apoptosis or DNA/siRNA to regulate oncogene expression. Here, a nanoparticle system that demonstrates an alternative approach to the treatment of cancers through the inhibition of cell invasion, while serving as a magnetic resonance and optical imaging contrast agent, is presented. The nanoparticle comprises an iron oxide nanoparticle core conjugated with an amine-functionalized poly(ethylene glycol) silane and a small peptide, chlorotoxin (CTX), which enables the tumor cell-specific binding of the nanoparticle. It is shown that the nanoparticle exhibits substantially enhanced cellular uptake and an invasion inhibition rate of ∼98% compared to unbound CTX (∼45%). Significantly, the investigation from flow cytometry analysis, transmission electron microscopy, and fluorescent imaging reveals that the CTX-enabled nanoparticles deactivated the membrane-bound matrix metalloproteinase 2 (MMP-2) and induced increased internalization of lipid rafts that contain surface-expressed MMP-2 and volume-regulating ion channels through receptor-mediated endocytosis, leading to enhanced prohibitory effects. Since upregulation and activity of MMP-2 have been observed in tumors of neuroectodermal origin, and in cancers of the breast, colon, skin, lung, prostate, ovaries, and a host of others, this nanoparticle system can be potentially used for non-invasive diagnosis and treatment of a variety of cancer types.

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