Department of Neurosurgery, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, People's Republic of China,
Department of Pathology, Clinical Medicine College, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.
Int J Nanomedicine. 2018 Aug 27;13:4781-4793. doi: 10.2147/IJN.S164364. eCollection 2018.
Gene therapy has recently shown considerable clinical benefit in cancer therapy during the past few years, and the application of this choice in cancer treatments is increasing continually. Gli1 is an ideal candidate target for cancer gene therapy and is important for tumorigenesis.
In this study, we developed a novel gene delivery system with a self-assembly method by using a 1,2-dioleoyl-3-trimethylammonium-propane and methoxy poly (ethylene glycol)-poly(lactide) copolymer (DMP), with zeta potential of 32.7 mV and measuring 35.6 nm. The effect of this delivery system was tested in vitro and in vivo.
DMP showed good performance in delivering siRNA to glioma cells in vitro with high transfection performance (98%). Moreover, DMP-Gli1si shows a satisfactory anti-glioma effect via induction of cell apoptosis and cell growth inhibition in vitro. Furthermore, for subcutaneous tumor-bearing mice, treatment with the DMP-Gli1si complex significantly inhibited tumor growth by inhibiting Gli1 protein expression, promoting apoptosis, and reducing proliferation.
The complex of Gli1 siRNA and DMP may potentially play an important role as a new drug in the clinical treatment of gliomas.
近年来，基因治疗在癌症治疗中显示出了相当大的临床益处，这种治疗方法在癌症治疗中的应用也在不断增加。Gli1 是癌症基因治疗的理想候选靶点，对肿瘤发生具有重要意义。
在这项研究中，我们开发了一种新的基因传递系统，采用自组装方法，使用 1,2-二油酰基-3-三甲铵丙烷和甲氧基聚乙二醇-聚（乳酸）共聚物（DMP），其 Zeta 电位为 32.7 mV，粒径为 35.6nm。在体外和体内测试了这种传递系统的效果。
DMP 在体外向神经胶质瘤细胞递送 siRNA 时表现出良好的性能，具有高转染效率（98%）。此外，DMP-Gli1si 通过诱导细胞凋亡和抑制细胞生长，在体外表现出令人满意的抗神经胶质瘤作用。此外，对于皮下荷瘤小鼠，DMP-Gli1si 复合物的治疗通过抑制 Gli1 蛋白表达、促进凋亡和减少增殖，显著抑制肿瘤生长。
Gli1 siRNA 和 DMP 的复合物可能作为一种新的药物在胶质细胞瘤的临床治疗中发挥重要作用。
