Theranostics 2017; 7(7):1942-1952. doi:10.7150/thno.16236

Research Paper

Mouse IP-10 Gene Delivered by Folate-modified Chitosan Nanoparticles and Dendritic/tumor Cells Fusion Vaccine Effectively Inhibit the Growth of Hepatocellular Carcinoma in Mice

Zixi Hu1*, Jiaojiao Chen1*, Sufang Zhou1*, Nuo Yang1, Siliang Duan1, Zhenghua Zhang1, Jing Su1, Jian He1, Zhiyong Zhang1, 2✉, Xiaoling Lu1✉, Yongxiang Zhao1✉

1. National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China;
2. Department of Surgery, Robert-Wood-Johnson Medical School University Hospital, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey 08901, USA.
* These authors contributed equally to this work.

Abstract

Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy. However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment. In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells. The combination of FA-chitosan/mIP-10 and DC/tumor cell fusion vaccine against hepatocellular carcinoma (HCC) effectively inhibited the growth of implanted HCC tumors and prolonged the survival of mice. The combination therapy significantly reduced myeloid-derived suppressor cells (MDSC) in mouse spleen, local tumor, and bone marrow while increasing tumor-specific IFN-γ responses. Furthermore, the combination therapy significantly inhibited tumor cell proliferation while promoting their apoptosis. Taken together, our data illustrate that the mIP-10 enhances the anti-tumor effect of DC/tumor cell fusion vaccine by alleviating the immunosuppressive tumor environment.

Keywords: DC/tumor fusion cell vaccines, interferon-induced protein-10, folic acid, chitosan.

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How to cite this article:
Hu Z, Chen J, Zhou S, Yang N, Duan S, Zhang Z, Su J, He J, Zhang Z, Lu X, Zhao Y. Mouse IP-10 Gene Delivered by Folate-modified Chitosan Nanoparticles and Dendritic/tumor Cells Fusion Vaccine Effectively Inhibit the Growth of Hepatocellular Carcinoma in Mice. Theranostics 2017; 7(7):1942-1952. doi:10.7150/thno.16236. Available from http://www.thno.org/v07p1942.htm