Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles

Omid Veiseh, Jonathan W. Gunn, Forrest M. Kievit, Conroy Sun, Chen Fang, Jerry S.H. Lee, Miqin Zhang

Research output: Contribution to journalArticle

132 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)256-264
Number of pages9
JournalSmall
Volume5
Issue number2
DOIs
StatePublished - Jan 19 2009

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Keywords

  • Antitumor agents
  • Biological materials
  • Cells
  • Imaging
  • Peptides

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

Cite this

Veiseh, O., Gunn, J. W., Kievit, F. M., Sun, C., Fang, C., Lee, J. S. H., & Zhang, M. (2009). Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles. Small, 5(2), 256-264. https://doi.org/10.1002/smll.200800646