International Journal of Nanomedicine (Aug 2018)
Delivery siRNA with a novel gene vector for glioma therapy by targeting Gli1
Abstract
Peizhi Zhou,1,* Yue Cao,2,* Xiaoxiao Liu,3 Ting Yu,3 Qian Xu,3 Chao You,1 Xiang Gao,1,3 Yuquan Wei2 1Department of Neurosurgery, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Pathology, Clinical Medicine College, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of China *These authors contributed equally to this work Background: 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. Methods: 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.Results: 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. Conclusion: The complex of Gli1 siRNA and DMP may potentially play an important role as a new drug in the clinical treatment of gliomas. Keywords: glioma, gene therapy, Gli1, MPEG-PLA, DOTAP
