title: Coupling of a bifunctional peptide R13 to OTMCS-PEI copolymer as a gene vector increases transfection efficiency and tumor targeting.
abstract: BACKGROUND
  A degradable polyethylenimine (PEI) derivative coupled to a bifunctional peptide R13 was developed to solve the transfection efficiency versus cytotoxicity and tumor-targeting problems of PEI when used as a gene vector.
  
  
  METHODS
  We crossed-linked low molecular weight PEI with N-octyl-N-quaternary chitosan (OTMCS) to synthesize a degradable PEI derivative (OTMCS-PEI), and then used a bifunctional peptide, RGDC-TAT (49-57) called R13 to modify OTMCS-PEI so as to prepare a new gene vector, OTMCS-PEI-R13. This new gene vector was characterized by various physicochemical methods. Its cytotoxicity and gene transfection efficiency were also determined both in vitro and in vivo.
  
  
  RESULTS
  The vector showed controlled degradation and excellent buffering capacity. The particle size of the OTMCS-PEI-R13/DNA complexes was around 150-250 nm and the zeta potential ranged from 10 mV to 30 mV. The polymer could protect plasmid DNA from being digested by DNase I at a concentration of 23.5 U DNase I/μg DNA. Further, the polymer was resistant to dissociation induced by 50% fetal bovine serum and 400 μg/mL sodium heparin. Compared with PEI 25 kDa, the OTMCS-PEI-R13/DNA complexes showed higher transfection efficiency both in vitro and in vivo. Further, compared with OTMCS-PEI, distribution of OTMCS-PEI-R13 at tumor sites was markedly enhanced, indicating the tumor-targeting specificity of R13.
  
  
  CONCLUSIONS
  OTMCS-PEI-R13 could be a potential candidate as a safe and efficient gene delivery carrier for gene therapy.
authors.affiliation: Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lv
authors.affiliation: Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Heilongjiang Forest By-Product and Speciality Institute, Mudanjiang, People's Republic of China.
authors.forename: Kewu
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, People's Republic of China.
authors.forename: Manman
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, People's Republic of China.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, People's Republic of China.
authors.forename: Kehai
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D002417:Cattle; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000008:administration & dosage*; D006367:HeLa Cells; D006801:Humans; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D036103:Nanotechnology; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D010316:Particle Size; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry; D014162:Transfection
chemical_list: D010455:Peptides; D011094:Polyethyleneimine; D048271:Chitosan
keywords: R13; nonviral gene vector; polyethylenimine; transfection efficiency; tumor-targeting