title: Theranostical nanosystem-mediated identification of an oncogene and highly effective therapy in hepatocellular carcinoma.
abstract: Because the primary surgical treatment options for hepatocellular carcinoma (HCC)-including hepatic resection and liver transplantation-often fail due to recurrence and metastasis, identifying early prognostic biomarkers and therapeutic targets for HCC is of great importance. This study shows that transducin β-like protein 1-related protein (TBLR1) is a key HCC oncogene that plays important roles in HCC proliferation, antiapoptosis, and angiogenesis by regulating the Wnt/β-catenin pathway. The folate-targeted theranostic small interfering RNA (siRNA) nanomedicine Fa-PEG-g-PEI-SPION/psiRNA-TBLR1 effectively silences the TBLR1 gene in different human HCC cell lines in vitro and in human HCC samples in vivo, resulting in the simultaneous suppression of HCC cell proliferation, antiapoptosis, and angiogenesis. Because of its multi-anticancer functions against HCC, intravenous injection of the folate-targeted siRNA nanomedicine into nude mice bearing intrahepatic or subcutaneous xenografts of human HCC has a significant therapeutic effect. Tumor growth in those animals was almost completely inhibited by treatment with Fa-PEG-g-PEI-SPION/psiRNA-TBLR1. Moreover, the SPION-encapsulated polyplexes possess high magnetic resonance imaging (MRI) detection sensitivity, which makes tumor-targeted siRNA delivery easily trackable using the clinical MRI technique.
  
  
  CONCLUSIONS
  The theranostic siRNA nanomedicine examined here possesses great theranostic potential for combined gene therapy and MRI diagnosis of HCC.
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, China.|Experimental Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Experimental Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Experimental Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Shunli
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Ruomi
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Hepatology Laboratory, Hospital for Liver Disease, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Chen
authors.affiliation: PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yiru
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Hepatology Laboratory, Hospital for Liver Disease, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Guihua
authors.initials: G
authors.lastname: Chen
authors.affiliation: PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xintao
authors.initials: X
authors.lastname: Shuai
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000235:genetics*; D009857:Oncogenes; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D011897:Random Allocation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C473691:TBL1XR1 protein, human