title: Pokemon siRNA Delivery Mediated by RGD-Modified HBV Core Protein Suppressed the Growth of Hepatocellular Carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a deadly human malignant tumor that is among the most common cancers in the world, especially in Asia. Hepatitis B virus (HBV) infection has been well established as a high risk factor for hepatic malignance. Studies have shown that Pokemon is a master oncogene for HCC growth, suggesting it as an ideal therapeutic target. However, efficient delivery system is still lacking for Pokemon targeting treatment. In this study, we used core proteins of HBV, which is modified with RGD peptides, to construct a biomimetic vector for the delivery of Pokemon siRNAs (namely, RGD-HBc-Pokemon siRNA). Quantitative PCR and Western blot assays revealed that RGD-HBc-Pokemon siRNA possessed the highest efficiency of Pokemon suppression in HCC cells. In vitro experiments further indicated that RGD-HBc-Pokemon-siRNA exerted a higher tumor suppressor activity on HCC cell lines, evidenced by reduced proliferation and attenuated invasiveness, than Pokemon-siRNA or RGD-HBc alone. Finally, animal studies demonstrated that RGD-HBc-Pokemon siRNA suppressed the growth of HCC xenografts in mice by a greater extent than Pokemon-siRNA or RGD-HBc alone. Based on the above results, Pokemon siRNA delivery mediated by RGD-modified HBV core protein was shown to be an effective strategy of HCC gene therapy.
authors.affiliation: 1 Faculty of Life Science & Chemical Engineering, Huaiyin Institute of Technology , Huai'an, Jiangsu, P.R. China .
authors.forename: Jing
authors.initials: J
authors.lastname: Kong
authors.affiliation: 1 Faculty of Life Science & Chemical Engineering, Huaiyin Institute of Technology , Huai'an, Jiangsu, P.R. China .
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.affiliation: 1 Faculty of Life Science & Chemical Engineering, Huaiyin Institute of Technology , Huai'an, Jiangsu, P.R. China .
authors.forename: Jianbo
authors.initials: J
authors.lastname: Jia
authors.affiliation: 2 Department of Hepatopancreatobiliary Surgery, Huai'an First People's Hospital, Nanjing Medical University , Huai'an, Jiangsu, P.R. China .
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: 3 Institute of Oceanology , Chinese Academy of Sciences, Qingdao, Shandong, P.R. China .
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.affiliation: 1 Faculty of Life Science & Chemical Engineering, Huaiyin Institute of Technology , Huai'an, Jiangsu, P.R. China .
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: 1 Faculty of Life Science & Chemical Engineering, Huaiyin Institute of Technology , Huai'an, Jiangsu, P.R. China .
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D006509:Hepatitis B / Q000503:physiopathology; D006512:Hepatitis B Core Antigens / Q000008:administration & dosage*; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy*; D008297:Male; D051379:Mice; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D014758:Viral Core Proteins / Q000008:administration & dosage*
chemical_list: D004268:DNA-Binding Proteins; D006512:Hepatitis B Core Antigens; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014758:Viral Core Proteins; C485514:ZBTB7A protein, human; C534392:p22 core protein, hepatitis B virus