title: Inhibiting metastasis of breast cancer cells in vitro using gold nanorod-siRNA delivery system.
abstract: Breast cancer is the most common malignant disease in women, and it is not the primary tumor but its metastasis kills most patients with breast cancer. Anti-metastasis therapy based on RNA interference (RNAi) is emerging as one of promising strategies in tumor therapy. However, construction of an efficient delivery system for siRNA is still one of the major challenges. In this work, siRNA against protease-activated receptor-1 (PAR-1) which is a pivotal gene involved in tumor metastasis was conjugated to gold nanorods (AuNRs) via electrostatic interaction and delivered to highly metastatic human breast cancer cells. It was demonstrated that the siRNA oligos were successfully delivered into the cancer cells and mainly located in vesicle-like structures including lysosome. After transfected with the complex of AuNRs and PAR-1 siRNA (AuNRs@PAR-1 siRNA), expression of PAR-1 at both mRNA and protein levels were efficiently down regulated, as evidenced by quantitative real time PCR and flow cytometry analysis, respectively. Transwell migration assay confirmed the decrease in metastatic ability of the cancer cells. The silencing efficiency of the complex was in-between that of TurboFect and Lipofectamine, however, the cytotoxicity of the AuNRs was lower than that of the latter two. Taken together, AuNRs with PAR-1 siRNA are suited for RNAi based anti-metastasis therapy.
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, P. R. China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Meng
authors.forename: Yinglu
authors.initials: Y
authors.lastname: Ji
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Kong
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Wu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006046:Gold / Q000737:chemistry*; D006801:Humans; D018613:Microscopy, Confocal; D043942:Nanotubes / Q000737:chemistry* / Q000633:toxicity; D009362:Neoplasm Metastasis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D010975:Platelet Aggregation Inhibitors
chemical_list: D004337:Drug Carriers; D034741:RNA, Small Interfering; D044463:Receptor, PAR-1; D006046:Gold; D010975:Platelet Aggregation Inhibitors