新型氧化石墨烯纳米粒子运载Stat3特异性shRNA生物靶向治疗实体肿瘤研究

项目名称： 新型氧化石墨烯纳米粒子运载Stat3特异性shRNA生物靶向治疗实体肿瘤研究

项目编号： No.81201188

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 郭宝锋

作者单位： 吉林大学

项目金额： 23万元

中文摘要： 氧化石墨烯制备方便，成本低廉，富含亲水基团，具有良好的生物相容性，是作为非病毒基因载体的良好材料。在前期工作中，我们研究了通过阻断肿瘤细胞中的Stat3通路，成功诱导肿瘤细胞的凋亡，抑制肿瘤细胞的生长。为突破RNA干涉的运载瓶颈，本研究拟在前期工作基础上，合成叶酸（FA）修饰的氧化石墨烯-聚乙烯亚胺-聚乙二醇（GO-PEI-PEG）纳米粒子，与乳腺癌细胞和肝癌细胞表面的叶酸受体特异性结合，探讨FA-GO-PEI-PEG作为Stat3-特异siRNA质粒运载体的可能性，结合氧化石墨烯吸收近红外线，产生热量杀伤肿瘤的特性，分别在体外和体内观察Stat3-siRNA靶向载体系统对肝癌和乳腺癌的靶向，从而达到抑制肝癌和乳腺癌生长的协同综合靶向治疗作用。

中文关键词： 氧化石墨烯；RNA干涉；Stat3；肝细胞癌；黑色素瘤

英文摘要： Graphene oxide (GO) possesses a good biocompatibility due to its rich hydrophilic groups. In addition, the production of GO can be achieved in a convenient, inexpensive and scalable way. Thus, GO is a promising candidate for efficient nonviral vector. In previous studies, we have applied a DNA vector-based Stat3-specific RNAi approach to block Stat3 signaling, and this procedure by inhibition of Stat3 and its related genes suppressed cancer growth induction of apoptosis. In order to seek a better RNA interference (RNAi) gene delivery, we are going to synthesize GO-PEI-PEG by covalent binding of folic acid (FA) molecules, thus allowing it to speci?cally target breast cancer cells and liver cancer cells with FA receptors. We explore the feasibility of GO as a nanovehicle for Stat3-specific RNAi gene delivery. We then utilize the strong optical absorbance of GO in the near-infrared (NIR) region for in vivo photothermal therapy, achieving ultraef?cient tumor ablation after intravenous administration of GO and low-power NIR laser irradiation on the tumor. Furthermore, in this work, we show much better therapeutic ef?cacy using targeted delivery in cancer treatment.

英文关键词： graphene oxide；RNA interference；Stat3；hepatocellular carcinoma；malignant melanoma