International Journal of Nanomedicine (Apr 2019)
Targeting EZH2 for glioma therapy with a novel nanoparticle–siRNA complex
Abstract
Xiang Wang,1 Yuanqi Hua,1 Guangya Xu,1 Senyi Deng,1 Daoke Yang,2 Xiang Gao1 1Department of Neurosurgery, Institute of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China; 2Tumor Hospital of First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China Background: For the past few years, gene-therapy has recently shown considerable clinical benefit in cancer therapy, and the applications of gene therapies in cancer treatments continue to increase perennially. EZH2, an ideal candidate for tumor gene therapy, plays an important role in the tumorigenesis. Methods: In this study, we developed a novel gene delivery system with a self-assembly method by Methoxy polyethylene glycol-polycaprolactone (MPEG-PCL) and DOTAP(DMC). And EZH2si-DMC was used to research anti-glioma both in vitro and in vivo. Results: DMC with zeta-potential value of 36.7 mV and size of 35.6 nm showed good performance in the delivery siRNA to glioma cell in vitro with high 98% transfection efficiency. EZH2si-DMC showed good anti-glioma effect in vitro through inducing cell apoptosis and inhibiting cell growth. What’s more, treatment of tumor-bearing mice with DMC-EZH2si complex had significantly inhibited tumor growth at the subcutaneous model in vivo by inhibiting EZH2 protein expression, promoting apoptosis and reducing proliferation. Conclusion: The EZH2 siRNA and DMC complex may be used to treat the glioma in clinical as a new drug. Keywords: glioma, gene therapy, EZH2, MPEG-PCL, DOTAP, tumorigenesis
