Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma

Forrest M Kievit, Omid Veiseh, Chen Fang, Narayan Bhattarai, Donghoon Lee, Richard G. Ellenbogen, Miqin Zhang

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

Glioma accounts for 80% of brain tumors and currently remains one of the most lethal forms of cancers. Gene therapy could potentially improve the dismal prognosis of patients with glioma but this treatment modality has not yet reached the bedside from the laboratory due to the lack of safe and effective gene delivery vehicles. In this study we investigate targeted gene delivery to C6 glioma cells in a xenograft mouse model using chlorotoxin (CTX) labeled nanoparticles. The developed nanovector consists of an iron oxide nanoparticle core, coated with a copolymer of chitosan, polyethylene glycol (PEG), and polyethylenimine (PEI). Green fluorescent protein (GFP) encoding DNA was bound to these nanoparticles, and CTX was then attached using a short PEG linker. Nanoparticles without CTX were also prepared as a control. Mice bearing C6 xenograft tumors were injected intravenously with the DNA-bound nanoparticles. Nanoparticle accumulation in the tumor site was monitored using magnetic resonance imaging and analyzed by histology, and GFP gene expression was monitored through Xenogen IVIS fluorescence imaging and confocal fluorescence microscopy. Interestingly, the CTX did not affect the accumulation of nanoparticles at the tumor site but specifically enhanced their uptake into cancer cells as evidenced by higher gene expression. These results indicate that this targeted gene delivery system may potentially improve treatment outcome of gene therapy for glioma and other deadly cancers.

Original languageEnglish (US)
Pages (from-to)4587-4594
Number of pages8
JournalACS Nano
Volume4
Issue number8
DOIs
StatePublished - Aug 24 2010

Fingerprint

genes
delivery
Genes
Nanoparticles
nanoparticles
Tumors
tumors
gene therapy
Gene therapy
gene expression
cancer
Green Fluorescent Proteins
Heterografts
Gene expression
Polyethylene glycols
mice
glycols
polyethylenes
DNA
Bearings (structural)

Keywords

  • Cancer
  • Chitosan
  • Chlorotoxin
  • Gene delivery
  • Iron oxide
  • Nanoparticle
  • Targeting

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Kievit, F. M., Veiseh, O., Fang, C., Bhattarai, N., Lee, D., Ellenbogen, R. G., & Zhang, M. (2010). Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma. ACS Nano, 4(8), 4587-4594. https://doi.org/10.1021/nn1008512

Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma. / Kievit, Forrest M; Veiseh, Omid; Fang, Chen; Bhattarai, Narayan; Lee, Donghoon; Ellenbogen, Richard G.; Zhang, Miqin.

In: ACS Nano, Vol. 4, No. 8, 24.08.2010, p. 4587-4594.

Research output: Contribution to journalArticle

Kievit, FM, Veiseh, O, Fang, C, Bhattarai, N, Lee, D, Ellenbogen, RG & Zhang, M 2010, 'Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma', ACS Nano, vol. 4, no. 8, pp. 4587-4594. https://doi.org/10.1021/nn1008512
Kievit FM, Veiseh O, Fang C, Bhattarai N, Lee D, Ellenbogen RG et al. Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma. ACS Nano. 2010 Aug 24;4(8):4587-4594. https://doi.org/10.1021/nn1008512
Kievit, Forrest M ; Veiseh, Omid ; Fang, Chen ; Bhattarai, Narayan ; Lee, Donghoon ; Ellenbogen, Richard G. ; Zhang, Miqin. / Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma. In: ACS Nano. 2010 ; Vol. 4, No. 8. pp. 4587-4594.
@article{3c8d8cdb28cb422f9a05210aa7ad42cb,
title = "Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma",
abstract = "Glioma accounts for 80{\%} of brain tumors and currently remains one of the most lethal forms of cancers. Gene therapy could potentially improve the dismal prognosis of patients with glioma but this treatment modality has not yet reached the bedside from the laboratory due to the lack of safe and effective gene delivery vehicles. In this study we investigate targeted gene delivery to C6 glioma cells in a xenograft mouse model using chlorotoxin (CTX) labeled nanoparticles. The developed nanovector consists of an iron oxide nanoparticle core, coated with a copolymer of chitosan, polyethylene glycol (PEG), and polyethylenimine (PEI). Green fluorescent protein (GFP) encoding DNA was bound to these nanoparticles, and CTX was then attached using a short PEG linker. Nanoparticles without CTX were also prepared as a control. Mice bearing C6 xenograft tumors were injected intravenously with the DNA-bound nanoparticles. Nanoparticle accumulation in the tumor site was monitored using magnetic resonance imaging and analyzed by histology, and GFP gene expression was monitored through Xenogen IVIS fluorescence imaging and confocal fluorescence microscopy. Interestingly, the CTX did not affect the accumulation of nanoparticles at the tumor site but specifically enhanced their uptake into cancer cells as evidenced by higher gene expression. These results indicate that this targeted gene delivery system may potentially improve treatment outcome of gene therapy for glioma and other deadly cancers.",
keywords = "Cancer, Chitosan, Chlorotoxin, Gene delivery, Iron oxide, Nanoparticle, Targeting",
author = "Kievit, {Forrest M} and Omid Veiseh and Chen Fang and Narayan Bhattarai and Donghoon Lee and Ellenbogen, {Richard G.} and Miqin Zhang",
year = "2010",
month = "8",
day = "24",
doi = "10.1021/nn1008512",
language = "English (US)",
volume = "4",
pages = "4587--4594",
journal = "ACS Nano",
issn = "1936-0851",
publisher = "American Chemical Society",
number = "8",

}

TY - JOUR

T1 - Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma

AU - Kievit, Forrest M

AU - Veiseh, Omid

AU - Fang, Chen

AU - Bhattarai, Narayan

AU - Lee, Donghoon

AU - Ellenbogen, Richard G.

AU - Zhang, Miqin

PY - 2010/8/24

Y1 - 2010/8/24

N2 - Glioma accounts for 80% of brain tumors and currently remains one of the most lethal forms of cancers. Gene therapy could potentially improve the dismal prognosis of patients with glioma but this treatment modality has not yet reached the bedside from the laboratory due to the lack of safe and effective gene delivery vehicles. In this study we investigate targeted gene delivery to C6 glioma cells in a xenograft mouse model using chlorotoxin (CTX) labeled nanoparticles. The developed nanovector consists of an iron oxide nanoparticle core, coated with a copolymer of chitosan, polyethylene glycol (PEG), and polyethylenimine (PEI). Green fluorescent protein (GFP) encoding DNA was bound to these nanoparticles, and CTX was then attached using a short PEG linker. Nanoparticles without CTX were also prepared as a control. Mice bearing C6 xenograft tumors were injected intravenously with the DNA-bound nanoparticles. Nanoparticle accumulation in the tumor site was monitored using magnetic resonance imaging and analyzed by histology, and GFP gene expression was monitored through Xenogen IVIS fluorescence imaging and confocal fluorescence microscopy. Interestingly, the CTX did not affect the accumulation of nanoparticles at the tumor site but specifically enhanced their uptake into cancer cells as evidenced by higher gene expression. These results indicate that this targeted gene delivery system may potentially improve treatment outcome of gene therapy for glioma and other deadly cancers.

AB - Glioma accounts for 80% of brain tumors and currently remains one of the most lethal forms of cancers. Gene therapy could potentially improve the dismal prognosis of patients with glioma but this treatment modality has not yet reached the bedside from the laboratory due to the lack of safe and effective gene delivery vehicles. In this study we investigate targeted gene delivery to C6 glioma cells in a xenograft mouse model using chlorotoxin (CTX) labeled nanoparticles. The developed nanovector consists of an iron oxide nanoparticle core, coated with a copolymer of chitosan, polyethylene glycol (PEG), and polyethylenimine (PEI). Green fluorescent protein (GFP) encoding DNA was bound to these nanoparticles, and CTX was then attached using a short PEG linker. Nanoparticles without CTX were also prepared as a control. Mice bearing C6 xenograft tumors were injected intravenously with the DNA-bound nanoparticles. Nanoparticle accumulation in the tumor site was monitored using magnetic resonance imaging and analyzed by histology, and GFP gene expression was monitored through Xenogen IVIS fluorescence imaging and confocal fluorescence microscopy. Interestingly, the CTX did not affect the accumulation of nanoparticles at the tumor site but specifically enhanced their uptake into cancer cells as evidenced by higher gene expression. These results indicate that this targeted gene delivery system may potentially improve treatment outcome of gene therapy for glioma and other deadly cancers.

KW - Cancer

KW - Chitosan

KW - Chlorotoxin

KW - Gene delivery

KW - Iron oxide

KW - Nanoparticle

KW - Targeting

UR - http://www.scopus.com/inward/record.url?scp=78650147756&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650147756&partnerID=8YFLogxK

U2 - 10.1021/nn1008512

DO - 10.1021/nn1008512

M3 - Article

VL - 4

SP - 4587

EP - 4594

JO - ACS Nano

JF - ACS Nano

SN - 1936-0851

IS - 8

ER -