A ligand-mediated nanovector for targeted gene delivery and transfection in cancer cells

Omid Veiseh, Forrest M. Kievit, Jonathan W. Gunn, Buddy D. Ratner, Miqin Zhang

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

As conventional cancer therapies struggle with toxicity issues and irregular remedial efficacy, the preparation of novel gene therapy vectors could offer clinicians the tools for addressing the genetic errors of diseased tissue. The transfer of gene therapy to the clinic has proven difficult due to safety, target specificity, and transfection efficiency concerns. Polyethylenimine (PEI) nanoparticles have been identified as promising gene carriers that induce gene transfection with high efficiency. However, the inherent toxicity of the material and non-selective delivery are the major concerns in applying these particles clinically. Here, a non-viral nanovector has been developed by PEGylation of DNA-complexing PEI in nanoparticles functionalized with an Alexa Fluor 647 near infrared fluorophore, and the chlorotoxin (CTX) peptide which binds specifically to many forms of cancer. With this nanovector, the potential toxicity to healthy cells is minimized by both the reduction of the toxicity of PEI with the biocompatible copolymer and the targeted delivery of the nanovector to cancer cells, as evaluated by viability studies. The nanovector demonstrated high levels of targeting specificity and gene transfection efficiency with both C6 glioma and DAOY medulloblastoma tumor cells. Significantly, with the CTX as the targeting ligand, the nanovector may serve as a widely applicable gene delivery system for a broad array of cancer types.

Original languageEnglish (US)
Pages (from-to)649-657
Number of pages9
JournalBiomaterials
Volume30
Issue number4
DOIs
StatePublished - Feb 1 2009

Fingerprint

Polyethyleneimine
Transfection
Genes
Ligands
Cells
Toxicity
Gene therapy
Neoplasms
Genetic Therapy
Nanoparticles
Fluorophores
Gene Transfer Techniques
Inborn Genetic Diseases
Medulloblastoma
Gene Targeting
Peptides
Tumors
DNA
Copolymers
Glioma

Keywords

  • Cancer targeting
  • Chlorotoxin
  • Gene therapy
  • Nanoparticle
  • Nanotechnology

ASJC Scopus subject areas

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

Cite this

A ligand-mediated nanovector for targeted gene delivery and transfection in cancer cells. / Veiseh, Omid; Kievit, Forrest M.; Gunn, Jonathan W.; Ratner, Buddy D.; Zhang, Miqin.

In: Biomaterials, Vol. 30, No. 4, 01.02.2009, p. 649-657.

Research output: Contribution to journalArticle

Veiseh, Omid ; Kievit, Forrest M. ; Gunn, Jonathan W. ; Ratner, Buddy D. ; Zhang, Miqin. / A ligand-mediated nanovector for targeted gene delivery and transfection in cancer cells. In: Biomaterials. 2009 ; Vol. 30, No. 4. pp. 649-657.
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