Date Published: December 29, 2017
Publisher: John Wiley and Sons Inc.
Author(s): Wei Zhao, Yuping Yang, Lingling Song, Tianyi Kang, Ting Du, Yujiao Wu, Meimei Xiong, Li Luo, Jianlin Long, Ke Men, Lan Zhang, Xiaoxin Chen, Meijuan Huang, Maling Gou.
Gene therapy provides a novel method for cancer therapy. This study shows a DNA nanocomplex that is inspired from vesicular stomatitis virus (VSV) for ovarian cancer therapy. This DNA nanocomplex consists of a cationized monomethoxy poly (ethylene glycol)‐poly (d,l‐lactide) (MPEG‐PLA) nanoparticle and a plasmid encoding the matrix protein of vesicular stomatitis virus (VSVMP) that plays a critical role in the VSV‐induced apoptosis of cancer cells. The cationized MPEG‐PLA nanoparticle that is self‐assembled by MPEG‐PLA copolymer and N‐[1‐(2,3‐dioleoyloxy) propyl]‐N,N,N‐trimethylammonium chloride (DOTAP) has low cytotoxicity and high transfection efficiency (>80%). Intraperitoneal administration of the pVSVMP nanocomplex remarkably inhibits the intraperitoneal metastasis of ovarian cancer and does not cause significant systemic toxicity. The apoptosis induction and anti‐angiogenesis are involved in the anticancer mechanism. This work demonstrates a VSV‐inspired DNA nanocomplex that has potential application for the treatment of intraperitoneal metastasis of ovarian cancer.
Epithelial ovarian carcinoma is the major cause of gynecologic cancer‐related death.1 Currently, the combination of surgical cytoreduction with subsequent platinum/taxane cytotoxic chemotherapy is the preferred therapeutic regimen for ovarian cancer therapy.2 However, the overall five‐year survival rate of advanced ovarian cancer (stage IIIC or IV [FIGO]) is less than 25% due to the drug resistance and cancer recurrence.[[qv: 2b,3]] Therefore, novel therapeutic strategies for ovarian cancer are under urgent desire.
Gene therapy has great promise for cancer treatment.[[qv: 6d]] In this work, we designed a VSV‐inspired pVSVMP nanocomplex for ovarian cancer therapy. Our results indicated that this pVSVMP nanocomplex could efficiently express VSVMP into ovarian cancer cells and induce cell death in vitro. Moreover, intraperitoneal administration of pVSVMP nanocomplex effectively inhibited the intraperitoneal metastasis of ovarian cancers in vivo, without causing significant systemic toxicity. These results demonstrated that the VSV‐inspired pVSVMP nanocomplex has a potential clinical application in ovarian cancer gene therapy.
Materials and Plasmids: Monomethoxy poly (ethylene glycol)‐poly (d,l‐lactide) (MPEG2000‐PLA2000, MW 4000), a diblock copolymer, was synthesized in the lab.29 Branched polyethylenimine (PEI, average molecular weight 25 kDa), N‐[1‐(2,3‐dioleoyloxy) propyl]‐N,N,N‐trimethylammonium chloride (DOTAP), MTT, Dulbecco’s modified Eagle’s medium (DMEM), and RPMI‐1640 medium were purchased from Sigma‐Aldrich (USA). The therapeutic gene (VSVMP) was previously constructed into pVAX expression vector (pVSVMP) in the lab,30 and pVAX was used as the empty vector.
The authors declare no conflict of interest.