Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma.
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.
Kievit
Forrest M
FM
Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
Veiseh
Omid
O
Fang
Chen
C
Bhattarai
Narayan
N
Lee
Donghoon
D
Ellenbogen
Richard G
RG
Zhang
Miqin
M
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004705:Endocytosis; D005290:Ferric Compounds / Q000737:chemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005910:Glioma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry*
D005290:Ferric Compounds; D011108:Polymers; D012604:Scorpion Venoms; C091539:Chlorotoxin; C000499:ferric oxide; D004247:DNA