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Nanoparticles co-delivering pVSVMP and pIL12 for synergistic gene therapy of colon cancer

Author:
Xiao, Yuanyuan, Yang, Yuping, Wu, Yujiao, Wang, Chunmei, Cheng, Hao, Zhao, Wei, Li, Yang, Liu, Beibei, Long, Jianlin, Guo, Wenhao, Gao, Guangping, Gou, Maling
Source:
RSC advances 2017 v.7 no.52 pp. 32613-32623
ISSN:
2046-2069
Subject:
Vesiculovirus, adverse effects, antineoplastic activity, apoptosis, biodegradability, colorectal neoplasms, electrostatic interactions, gene therapy, genes, immune response, interleukin-12, intraperitoneal injection, metastasis, nanoparticles, neoplasm cells, plasmids
Abstract:
Nanoparticles delivering therapeutic genes have promising applications in cancer treatments. Here, we used biodegradable heparin–polyethyleneimine (HPEI) nanoparticles to co-deliver two genes (vesicular stomatitis virus matrix protein, VSVMP; interleukin-12, IL12) for cancer therapy. These HPEI nanoparticles can bind the plasmid expressing VSVMP (pVSVMP) and the plasmid expressing IL12 (pIL12) through electrostatic interactions, and mediate the simultaneous expression of VSVMP and IL12 in colon cancer cells in vitro and in vivo. After intraperitoneal administration, the HPEI/pIL12 + pVSVMP complexes efficiently inhibit the growth of intraperitoneal metastasis of C-26 colon cancer, showing synergistic anticancer efficacy, without obvious systemic adverse effects. While VSVMP induces apoptosis, VSVMP and IL12 synergistically generate an anticancer immune response, which renders the potent anticancer effect of HPEI/pIL12 + pVSVMP. Our data suggest that VSVMP and IL12 could synergistically inhibit cancer survival in vivo, and the HPEI nanoparticle co-delivered VSVMP and IL12 might have potential application in treating intraperitoneal metastasis of colon cancer.
Agid:
6419650