title: Folate-linked lipoplexes for short hairpin RNA targeting claudin-3 delivery in ovarian cancer xenografts.
abstract: Ovarian cancers highly overexpress folate receptor α (FRα) and claudin3 (CLDN3), both of which are associated with tumor progression and poor prognosis of patients. Downregulation of FRα and CLDN3 in ovarian cancer may suppress tumor growth and promote benign differentiation of tumor. In this study, F-P-LP/CLDN3, a FRα targeted liposome loading with short hairpin RNA (shRNA) targeting CLDN3 was prepared and the pharmaceutical properties were characterized. Then, the antitumor effect of F-P-LP/CLDN3 was studied in an in vivo model of advanced ovarian cancer. Compared with Control, F-P-LP/CLDN3 promoted benign differentiation of tumor and achieved about 90% tumor growth inhibition. In the meantime, malignant ascites production was completely inhibited, and tumor nodule number and tumor weight were significantly reduced (p<0.001). FRα and CLDN3 were downregulated together in tumor tissues treated by F-P-LP/CLDN3. The antitumor mechanisms were achieved by promoting tumor cell apoptosis, inhibiting tumor cell proliferation and reducing microvessel density. Finally, safety evaluation indicated that F-P-LP/CLDN3 was a safe formulation in intraperitoneally administered cancer therapy. We come to a conclusion that F-P-LP/CLDN3 is a potential targeting formulation for ovarian cancer gene therapy.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Zhi-Yao
authors.initials: ZY
authors.lastname: He
authors.forename: Xia-Wei
authors.initials: XW
authors.lastname: Wei
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.forename: Shun-Tao
authors.initials: ST
authors.lastname: Luo
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Yi-Yi
authors.initials: YY
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Cui-Cui
authors.initials: CC
authors.lastname: Ma
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.forename: Fu-Chun
authors.initials: FC
authors.lastname: Guo
authors.forename: Ting-Hong
authors.initials: TH
authors.lastname: Ye
authors.forename: Hua-Shan
authors.initials: HS
authors.lastname: Shi
authors.forename: Guo-Bo
authors.initials: GB
authors.lastname: Shen
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Feng-Ming
authors.initials: FM
authors.lastname: Gong
authors.forename: Gu
authors.initials: G
authors.lastname: He
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiang-Rong
authors.initials: XR
authors.lastname: Song
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
mesh_terms: D000818:Animals; D001940:Breast / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D062465:Claudin-3 / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D014162:Transfection
chemical_list: D062465:Claudin-3; D034741:RNA, Small Interfering; D005492:Folic Acid
keywords: Claudin3; Folate receptor α; Gene therapy; Lipoplex; Ovarian cancer