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

A ligand-mediated nanovector for targeted gene delivery and transfection in cancer cells.
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DOI:
10.1016/j.biomaterials.2008.10.003
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发表时间:
2009-02
期刊:
影响因子:
14
通讯作者:
Zhang, Miqin
Zhang, Miqin
中科院分区:
工程技术1区
文献类型:
--
作者:
Veiseh, Omid;Kievit, Forrest M.;Gunn, Jonathan W.;Ratner, Buddy D.;Zhang, Miqin

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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.
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