title: Therapeutic efficiency of folated poly(ethylene glycol)-chitosan-graft-polyethylenimine-Pdcd4 complexes in H-ras12V mice with liver cancer.
abstract: BACKGROUND
  Chitosan and chitosan derivatives have been proposed as alternative and biocompatible cationic polymers for nonviral gene delivery. However, the low transfection efficiency and low specificity of chitosan is an aspect of this approach that must be addressed prior to any clinical application. In the present study, folated poly(ethylene glycol)-chitosan-graft-polyethylenimine (FPCP) was investigated as a potential folate receptor-overexpressed cancer cell targeting gene carrier.
  
  
  METHODS
  The FPCP copolymer was synthesized in two steps. In the first step, folate-PEG was synthesized by an amide formation reaction between the activated carboxyl groups of folic acid and the amine groups of bifunctional poly(ethylene glycol) (PEG). In the second step, FPCP was synthesized by an amide formation reaction between the activated carboxyl groups of folate-PEG and amine groups of CHI-g-polyethyleneimine (PEI). The composition of FPCP was characterized by ¹H nuclear magnetic resonance.
  
  
  RESULTS
  FPCP showed low cytotoxicity in various cell lines, and FPCP-DNA complexes showed good cancer cell specificity as well as good transfection efficiency in the presence of serum. Further, FPCP-Pdcd4 complexes reduced tumor numbers and progression more effectively than PEI 25 kDa in H-ras12V liver cancer mice after intravenous administration.
  
  
  CONCLUSIONS
  Our data suggest that FPCP, which has improved transfection efficiency and cancer cell specificity, may be useful in gene therapy for liver cancer.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: You-Kyoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Arash
authors.initials: A
authors.lastname: Minai-Tehrani
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology*; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011905:Genes, ras; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D051017:Apoptosis Regulatory Proteins; D004337:Drug Carriers; D016601:RNA-Binding Proteins; C551320:chitosan-graft-polyethylenimine; C552831:poly(ethylene glycol)-folate; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan; D005492:Folic Acid
keywords: efficiency; folated poly(ethylene glycol)-chitosan-graft-polyethylenimine; liver cancer; safety; targeted gene therapy