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

• Published in: International journal of nanomedicine 2016-01, Vol.11 (Issue 1), p.501-512
• Main Authors: Luo, Li, Du, Ting, Zhang, Jiumeng, Zhao, Wei, Cheng, Hao, Yang, Yuping, Wu, Yujiao, Wang, Chunmei, Men, Ke, Gou, Maling
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Anticoagulants; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Apoptosis Regulatory Proteins - administration & dosage; Apoptosis Regulatory Proteins - genetics; Brain cancer; Cancer genetics; Cancer prevention; Cancer therapies; Cancer treatment; Deoxyribonucleic acid; DNA; Female; Gene expression; Gene therapy; Genes; Genetic aspects; Genetic Therapy - methods; Health aspects; Heparin - chemistry; Heparin-polyethyleneimine nanoparticles; Human survivin T34A; Humans; Injections, Intraperitoneal; Laboratories; Lung cancer; Mice, Inbred BALB C; Molecular weight; Morphology; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Original Research; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Ovarian Neoplasms - therapy; Plasmids - genetics; Polyethyleneimine - chemistry; Rats, Sprague-Dawley; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - genetics; tat Gene Products, Human Immunodeficiency Virus - administration & dosage; tat Gene Products, Human Immunodeficiency Virus - genetics; Tissue Distribution; Vectors (Biology); Xenograft Model Antitumor Assays
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S93496

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.