Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma.
Chlorotoxin labeled magnetic nanovectors for targeted gene delivery to glioma.
复制标题
DOI：
10.1021/nn1008512
复制
发表时间：
2010-08-24
期刊：
影响因子：
17.1
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Kievit FM;Veiseh O;Fang C;Bhattarai N;Lee D;Ellenbogen RG;Zhang M
神经胶质瘤占脑肿瘤的80%，目前仍然是最致命的癌症之一。基因治疗可以潜在地改善胶质瘤患者的预后，但由于缺乏安全有效的基因递送载体，这种治疗方式尚未从实验室到达床边。在这项研究中，我们研究了在异种移植小鼠模型中使用氯毒素（CTX）标记的纳米颗粒向C6胶质瘤细胞的靶向基因递送。开发的纳米载体由氧化铁纳米颗粒核心组成，包覆有壳聚糖、聚乙二醇（PEG）和聚乙烯亚胺（PEI）的共聚物。编码绿色荧光蛋白（GFP）的DNA与这些纳米颗粒结合，然后使用短的PEG接头连接CTX。也制备不含CTX的纳米颗粒作为对照。携带C6异种移植肿瘤的小鼠静脉内注射DNA结合的纳米颗粒。使用磁共振成像监测肿瘤部位中的纳米颗粒积聚并通过组织学分析，通过Xenogen IVIS荧光成像和共聚焦荧光显微镜监测GFP基因表达。有趣的是，CTX并不影响纳米颗粒在肿瘤部位的积累，但特异性地增强了它们进入癌细胞的吸收，这一点由更高的基因表达所证明。这些结果表明，这种靶向基因递送系统可能会潜在地改善神经胶质瘤和其他致命癌症的基因治疗的治疗效果。
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.
登录
查看更多内容
影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
DOI：
10.2217/17435889.3.5.703
发表时间：
2008-10
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Longmire M;Choyke PL;Kobayashi H
通讯作者：
Kobayashi H
影响因子：
13.3
作者：
Kohler, N;Sun, C;Zhang, MQ
通讯作者：
Zhang, MQ
影响因子：
19
作者：
Kievit, Forrest M.;Veiseh, Omid;Bhattarai, Narayan;Fang, Chen;Gunn, Jonathan W.;Lee, Donghoon;Ellenbogen, Richard G.;Olson, James M.;Zhang, Miqin
通讯作者：
Zhang, Miqin