title: Anti-tumor immune response of folate-conjugated chitosan nanoparticles containing the IP-10 gene in mice with hepatocellular carcinoma.
abstract: Immunotherapy is one of the most promising new therapies for hepatocellular carcinoma (HCC) in recent years. In this study, folate-conjugated chitosan nanoparticles (FA-CS-NPs) were loaded with mouse interferon-γ-inducible protein-10 (IP-10) plasmid, which were used for immunotherapy in HCC. H22 tumor-bearing mice were treated with FA-CS-NPs entrapped IP-10 plasmid and targeting efficiency was observed by optical imaging in vivo. Flow cytometry was used to measure the number of myeloid-derived suppressor cells (MDSCs) in the tumor and CD4+CD25+FoxP3+ T-regulatory cells (CD4+CD25+FoxP3+ Tregs) in the spleen. The enzyme-linked immunospot (ELISPOT) assay was used to quantify the number of interferon-γ (IFN-γ)-positive cells. IP-10 expression, tumor vessel density, cell proliferation and apoptosis were evaluated by immunohistochemistry. It was shown that FA-CS-NPs entrapped IP-10 plasmid displayed anti-tumor activity with inhibition of tumor growth and prolonging the survival time in H22 tumor-bearing mice. Treatment of H22 tumor-bearing mice with FA-CS-NPs entrapped IP-10 plasmid inhibited angiogenesis and promoted IP-10 expression and induced apoptosis in the tumor. FA-CS-NPs entrapped IP-10 plasmid-treated mice also had a lower proportion of Tregs in the spleen, a higher proportion of MDSCs in the tumor and higher number of IFN-γ-positive cells in the spleen compared with the mice from the other experimental groups. These data suggested that the gene delivery system of folate-conjugated chitosan nanoparticle loaded with IP-10 plasmid may be a promising strategy for immunotherapy of HCC.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Lai
authors.forename: Xia
authors.initials: X
authors.lastname: Yu
authors.forename: Huiqin
authors.initials: H
authors.lastname: Zhuo
authors.forename: Nuo
authors.initials: N
authors.lastname: Zhou
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xie
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.forename: Yi
authors.initials: Y
authors.lastname: Peng
authors.forename: Xiaoxun
authors.initials: X
authors.lastname: Xie
authors.forename: Guorong
authors.initials: G
authors.lastname: Luo
authors.forename: Sufang
authors.initials: S
authors.lastname: Zhou
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology*; D048271:Chitosan / Q000737:chemistry*; D006224:Cricetinae; D004247:DNA / Q000008:administration & dosage*; D005260:Female; D005492:Folic Acid / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D017471:Receptors, Interferon / Q000276:immunology*; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome; D000096743:Interferon gamma Receptor
chemical_list: D054357:Chemokine CXCL10; D048271:Chitosan; D004247:DNA; D005492:Folic Acid; D053769:Nanocapsules; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C485433:Cxcl10 protein, mouse