Targeting EZH2 for glioma therapy with a novel nanoparticle-siRNA complex

利用新型纳米粒子-siRNA 复合物靶向 EZH2 进行胶质瘤治疗

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作者:Xiang Wang, Yuanqi Hua, Guangya Xu, Senyi Deng, Daoke Yang, Xiang Gao

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.

Conclusion

The EZH2 siRNA and DMC complex may be used to treat the glioma in clinical as a new drug.

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.

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