title: Targeted hepatocellular carcinoma therapy: transferrin modified, self-assembled polymeric nanomedicine for co-delivery of cisplatin and doxorubicin.
abstract: BACKGROUND
  Targeted hepatocellular carcinoma (HCC) therapy was carried out to improve the efficacy of liver cancers. The aim of this study was to develop transferrin (Tf) modified, self-assembled polymeric nanoparticles for co-delivery doxorubicin (DOX) and cisplatin (DDP), to achieve combination tumor therapy.
  
  
  METHODS
  Tf modified polyethylene glycol (PEG) containing DOX prodrug (Tf-PEG-DOX) was synthesized. DDP containing poly(lactic-co-glycolic) acid (PLGA) materials (PLGA-DDP) were prepared. Tf modified DOX and DDP loaded PLGA nanoparticles (Tf-DOX/DDP NPs) were prepared by using nanoprecipitation method. The particles sizes, zeta potentials, drug loading effects were characterized. The cytotoxicity of the NPs was evaluated in human hepatoma carcinoma cell lines (HepG2 cells), and in vivo anti-tumor was observed in mice bearing human HepG2 cells model.
  
  
  RESULTS
  Tf-DOX/DDP NPs displayed higher cytotoxicity and enhanced antitumor activity both in vitro and in vivo over their non-modified and single drug loaded counterparts.
  
  
  CONCLUSIONS
  Tf-DOX/DDP NPs can achieve outstanding anti-tumor activity due to the combination effect of two drugs and the active targeting ability of Tf ligands. The self-assembled polymeric nanomedicine could act as an efficient therapy method for HCC treatment.
authors.affiliation: a Ji'nan Central Hospital Affiliated to Shandong University , Ji'nan , People's Republic of China ;
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Zhang
authors.affiliation: b Department of Pharmacy , Binzhou People ' s Hospital , Binzhou , People's Republic of China ;
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Li
authors.affiliation: c Department of Pharmacy , Qingdao Municipal Hospital , Qingdao , People's Republic of China.
authors.forename: Meixing
authors.initials: M
authors.lastname: Yan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008024:Ligands; D008113:Liver Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D051379:Mice; D050997:Nanomedicine / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011355:Prodrugs / Q000138:chemical synthesis* / Q000627:therapeutic use; D014168:Transferrin / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D011355:Prodrugs; D014168:Transferrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002945:Cisplatin
keywords: Combination chemotherapy; hepatocellular carcinoma; multidrug resistance; prodrug; synergistic effect