Folate-linked lipoplexes for short hairpin RNA targeting claudin-3 delivery in ovarian cancer xenografts

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,...

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Bibliographic Details
Published in:Journal of controlled release 2013-12, Vol.172 (3), p.679-689
Main Authors: He, Zhi-Yao, Wei, Xia-Wei, Luo, Min, Luo, Shun-Tao, Yang, Yang, Yu, Yi-Yi, Chen, Yan, Ma, Cui-Cui, Liang, Xiao, Guo, Fu-Chun, Ye, Ting-Hong, Shi, Hua-Shan, Shen, Guo-Bo, Wang, Wei, Gong, Feng-Ming, He, Gu, Yang, Li, Zhao, Xia, Song, Xiang-Rong, Wei, Yu-Quan
Format: Article
Language:English
Subjects:
animal ovaries
Animals
apoptosis
ascites
Breast - metabolism
Breast - pathology
Cell Line, Tumor
cell proliferation
Claudin-3 - genetics
Claudin3
Female
Folate receptor α
folic acid
Folic Acid - chemistry
Gene Expression Regulation, Neoplastic
Gene therapy
Genetic Therapy
growth retardation
Humans
Lipoplex
Mice, Inbred BALB C
Mice, Nude
neoplasm cells
Ovarian cancer
ovarian neoplasms
Ovarian Neoplasms - genetics
Ovarian Neoplasms - pathology
Ovarian Neoplasms - therapy
patients
prognosis
RNA Interference
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - genetics
RNA, Small Interfering - therapeutic use
small interfering RNA
tissues
Transfection
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Summary: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
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2013.10.015