Chlorotoxin bound magnetic nanovector tailored for cancer cell targeting, imaging, and siRNA delivery

Omid Veiseh, Forrest M. Kievit, Chen Fang, Ni Mu, Soumen Jana, Matthew C. Leung, Hyejung Mok, Richard G. Ellenbogen, James O. Park, Miqin Zhang

Research output: Contribution to journalArticle

131 Scopus citations

Abstract

Ribonucleic acid interference (RNAi) is a powerful molecular tool that has potential to revolutionize the treatment of cancer. One major challenge of applying this technology for clinical application is the lack of site-specific carriers that can effectively deliver short interfering RNA (siRNA) to cancer cells. Here we report the development and assessment of a cancer-cell specific magnetic nanovector construct for efficient siRNA delivery and non-invasive monitoring through magnetic resonance imaging (MRI). The base of the nanovector construct is comprised of a superparamagnetic iron oxide nanoparticle core coated with polyethylene glycol (PEG)-grafted chitosan, and polyethylenimine (PEI). The construct was then further functionalized with siRNA and a tumor-targeting peptide, chlorotoxin (CTX), to improve tumor specificity and potency. Flow cytometry, quantitative RT-PCR, and fluorescence microscopy analyses confirmed receptor-mediated cellular internalization of nanovectors and enhanced gene knockdown through targeted siRNA delivery. The ability of this nanovector construct to generate specific contrast enhancement of glioblastoma cells was demonstrated through MR imaging. These findings suggest that this CTX enabled nanoparticle carrier may be well suited for delivery of RNAi therapeutics to brain cancer cells.

Original languageEnglish (US)
Pages (from-to)8032-8042
Number of pages11
JournalBiomaterials
Volume31
Issue number31
DOIs
Publication statusPublished - Nov 1 2010

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Keywords

  • Cancer
  • Gene therapy
  • Glioma
  • MRI
  • Nanoparticle
  • SiRNA

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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