Int J Nanomedicine 2011 ;6 2419-27. [IF:4.976]
Gene therapy for C-26 colon cancer using heparin-polyethyleneimine nanoparticle-mediated survivin T34A.
Zhang L , Gao X , Men K , Wang B , Zhang S , Qiu J , Huang M , Gou M , Huang N , Qian Z , Zhao X , Wei Y .
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, People's Republic of China.
四川大学华西医院生物治疗国家重点实验室
Abstract
Gene therapy provides a novel method for the prevention and treatment of cancer, but the clinical application of gene therapy is restricted, mainly because of the absence of an efficient and safe gene delivery system. Recently, we developed a novel nonviral gene carrier, ie, heparin-polyethyleneimine (HPEI) nanoparticles for this purpose. HPEI nanoparticles were used to deliver plasmid-expressing mouse survivin-T34A (ms-T34A) to treat C-26 carcinoma in vitro and in vivo. According to the in vitro studies, HPEI nanoparticles could efficiently transfect the pGFP report gene into C-26 cells, with a transfection efficiency of 30.5% ± 2%. Moreover, HPEI nanoparticle-mediated ms-T34A could efficiently inhibit the proliferation of C-26 cells by induction of apoptosis in vitro. Based on the in vivo studies, HPEI nanoparticles could transfect the Lac-Z report gene into C-26 cells in vivo. Intratumoral injection of HPEI nanoparticle-mediated ms-T34A significantly inhibited growth of subcutaneous C-26 carcinoma in vivo by induction of apoptosis and inhibition of angiogenesis. This research suggests that HPEI nanoparticle-mediated ms-T34A may have a promising role in C-26 colon carcinoma therapy.
摘要：
基因治疗对于癌症的预防和治疗提供了新的方法，但是在临床上基因治疗的应用还是很有限，主要是因为缺乏有效和安全的基因导入系统。最近，为此我们发现了一种新的非病毒基因载体，即肝素-聚乙烯纳米。肝素-聚乙烯纳米用于输送质粒表达的老鼠生存素，T34A，用于在体内和体外治疗C-26结肠癌。根据在体外研究，肝素-聚乙烯纳米能有效地将pGFP报告的基因转染进入C-26细胞,转染有效率达30.5% ± 2%。还有，肝素-聚乙烯纳米介导的生存素T34A可通过在体外诱导细胞凋亡从而有效抑制C-26细胞的繁殖。在体外研究的基础上，肝素-聚乙烯纳米在体内也可将Lac-Z报告基因转染入C-26细胞。瘤内注射肝素-聚乙烯纳米介导的生存素T34A在体内可通过诱导细胞凋亡或抑制血管生成进而有效抑制皮下C-26瘤细胞的生长。本研究暗示肝素-聚乙烯纳米介导的生存素T34A 可能在C-26结肠癌的治疗发挥很有前途的作用。
