title: Folate-Modified Lipoplexes Delivering the Interleukin-12 Gene for Targeting Colon Cancer Immunogene Therapy.
abstract: The incidence and mortality rate of colorectal cancer increase every year, making it a serious threat to human health. Targeted immunogene therapy is a novel method of treating this type of cancer. Colon cancer overexpresses folate receptor α (FRα) and folate-modified liposomes for colon cancer immunogene therapy may suppress tumor growth effectively. In this study, F-PLP/pIL12, an FRα-targeted lipoplex loading plasmid interleukin-12 (pIL12) was prepared and its physicochemical properties were characterized. Then the antitumor effect of F-PLP/pIL12 was studied in an in vivo model of CT-26 colon cancer. F-PLP/pIL12 was associated with about 56.6% tumor growth inhibition compared with the saline control. The production of malignant ascites was significantly less pronounced than in controls, and there were fewer tumor nodules and less overall tumor mass (P < 0.01). There was more IL12 expression and IFN-γ secretion in F-PLP/pIL12-treated tumor tissues, but there was less FRα expression. The antitumor mechanisms involved inducing tumor cell apoptosis, reducing microvessel density, and stimulating TNF-α secretion. In addition, there were fewer M2 macrophages in the tumor microenvironment of tissues stimulated with F-PLP/pIL12, which also activated the natural killer cells. H&E staining of vital organs suggested that F-PLP/pIL12 is safe for use in intraperitoneally administered cancer therapy. It was here concluded that F-PLP/plL12 may be a suitable targeting formulation for colon cancer immunogene therapy.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.forename: Shun-Tao
authors.initials: ST
authors.lastname: Luo
authors.forename: Xia-Wei
authors.initials: XW
authors.lastname: Wei
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Cui-Cui
authors.initials: CC
authors.lastname: Ma
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Yang
authors.forename: Bi-Lan
authors.initials: BL
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Xiang-Rong
authors.initials: XR
authors.lastname: Song
authors.forename: Zhi-Yao
authors.initials: ZY
authors.lastname: He
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D016503:Drug Delivery Systems; D058975:Folate Receptor 1 / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D007167:Immunotherapy / Q000379:methods*; D018664:Interleukin-12 / Q000235:genetics*; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D051379:Mice
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D058975:Folate Receptor 1; D008081:Liposomes; D018664:Interleukin-12; D005492:Folic Acid