title: Biodistribution of TAT-LHRH conjugated chitosan/DNA nanoparticles in the mice bearing hepatoma xenografts.
abstract: Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy and the third leading cause of cancer-related deaths worldwide. More effective cures for HCC patients are urgently needed, of which gene therapy is among those with the most potential. We previously developed a novel gene carrier by conjugating low molecular weight chitosan with TAT (transactivator of transcription) peptide and LHRH (luteinizing hormone-releasing hormone) analog, with the resultant TAT-LHRH-chitosan conjugate (TLC) demonstrating high selectivity for hepatoma cells in vitro. However, it remains unclear whether TLC can deliver the genes to the target organs and tissues in vivo, which is one of the critical features determining their medical application potential. The current study further investigated the in vivo distribution of TLC/DNA nanoparticles (TLCDNPs) in the nude mice with subcutaneous hepatoma xenografts. It was found that TLCDNPs delayed the renal clearance of DNA and prolonged its circulation time as compared with CS/DNA complexes (CDNPs) and naked DNA, but failed to demonstrate enhanced accumulation of DNA in the hepatoma xenografts. The mechanisms regarding the failure of TLCDNPs' tumor targeting in the mice bearing subcutaneous hepatoma xenografts remain unclear and need to be further addressed. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2394-2400, 2016.
authors.affiliation: Lab of Bioengineering, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin, 300192, China.
authors.forename: Lanxia
authors.initials: L
authors.lastname: Liu
authors.affiliation: Lab of Bioengineering, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin, 300192, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gynecology, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, 300100, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Stomatology, Tianjin First Central Hospital, Tianjin, 300192, China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Duan
authors.affiliation: Lab of Bioengineering, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin, 300192, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Dong
authors.affiliation: Lab of Bioengineering, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin, 300192, China.
authors.forename: Dunwan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Gynecology, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, 300100, China.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Lab of Bioengineering, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin, 300192, China.
authors.forename: Xigang
authors.initials: X
authors.lastname: Leng
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D048271:Chitosan / Q000031:analogs & derivatives*; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D015696:Gene Products, tat / Q000737:chemistry; D018014:Gene Transfer Techniques; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D015696:Gene Products, tat; D007987:Gonadotropin-Releasing Hormone; D004247:DNA; D048271:Chitosan
keywords: LHRH; TAT; chitosan; gene therapy; hepatocellular carcinoma; nanoparticles