Efficient inhibition of ovarian cancer by degradable nanoparticle-delivered survivin T34A gene

Abstract

Li Luo,1,* Ting Du,1,* Jiumeng Zhang,1 Wei Zhao,2 Hao Cheng,1 Yuping Yang,1 Yujiao Wu,1 Chunmei Wang,1 Ke Men,1 Maling Gou1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, 2Department of Thoracic Oncology, Cancer Center, West China Hospital, Medical School, Sichuan University, Chengdu, People’s Republic of China *These authors contributed equally to this work Abstract: Gene therapy has promising applications in ovarian cancer therapy. Blocking the function of the survivin protein could lead to the growth inhibition of cancer cells. Herein, we used degradable heparin–polyethyleneimine (HPEI) nanoparticles to deliver a dominant-negative human survivin T34A (hs-T34A) gene to treat ovarian cancer. HPEI nanoparticles were characterized and were found to have a dynamic diameter of 66±4.5 nm and a zeta potential of 27.1±1.87 mV. The constructed hs-T34A gene expression plasmid could be effectively delivered into SKOV3 ovarian carcinoma cells by HPEI nanoparticles with low cytotoxicity. Intraperitoneal administration of HPEI/hs-T34A complexes could markedly inhibit tumor growth in a mouse xenograft model of SKOV3 human ovarian cancer. Moreover, according to our results, apparent apoptosis of cancer cells was observed both in vitro and in vivo. Taken together, the prepared HPEI/hs-T34A formulation showed potential applications in ovarian cancer gene therapy. Keywords: human survivin T34A, heparin–polyethyleneimine nanoparticles, gene therapy, ovarian cancer

Keywords

• Human survivin T34A
• Heparin-polyethyleneimine nanoparticles
• Gene therapy
• Ovarian cancer