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

129 Citations (Scopus)

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

Fingerprint

Nanoparticles
Tumors
Neoplasms
Matrix Metalloproteinase 2
Contrast Media
Neuroectodermal Tumors
Cells
Imaging techniques
Chlorotoxin
Oncology
Flow cytometry
Optical Imaging
Cell death
Magnetic resonance
Therapeutics
Endocytosis
Transmission Electron Microscopy
Silanes
Drug delivery
Iron oxides

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

Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles. / Veiseh, Omid; Gunn, Jonathan W.; Kievit, Forrest M.; Sun, Conroy; Fang, Chen; Lee, Jerry S.H.; Zhang, Miqin.

In: Small, Vol. 5, No. 2, 19.01.2009, p. 256-264.

Research output: Contribution to journalArticle

Veiseh, O, Gunn, JW, Kievit, FM, Sun, C, Fang, C, Lee, JSH & Zhang, M 2009, 'Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles', Small, vol. 5, no. 2, pp. 256-264. https://doi.org/10.1002/smll.200800646
Veiseh, Omid ; Gunn, Jonathan W. ; Kievit, Forrest M. ; Sun, Conroy ; Fang, Chen ; Lee, Jerry S.H. ; Zhang, Miqin. / Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles. In: Small. 2009 ; Vol. 5, No. 2. pp. 256-264.
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