title: Evaluation of transferrin-polyethylenimine conjugate for targeted gene delivery.
abstract: With the aim to improve the specificity and to reduce the cytotoxicity of polyethylenimine (PEI), we have synthesized the conjugates of the branched PEI (25 kDa) with transferrin. The transferrin-PEI (TP) conjugates with five compositions were synthesized using periodate oxidation method and confirmed by FT-IR spectroscopy and gel permeation chromatography. The free amine contents of TP conjugates, which were able to condense and deliver DNA, increased as the amount of PEI increased. TP/DNA polyplexes were characterized by measuring gel electrophoresis, ethidium bromide fluorescence quenching, particle size and zeta potential of complexes. Complete complexation of the polyplexes was observed above the N/P ratio of 5 in TP/ DNA, and above 3 in PEI/DNA, respectively. The zeta potential of the complexes decreased as the amount of transferrin in TP conjugates increased. Transfection efficiency of TP conjugates was evaluated in HeLa cell and Jurkat cell systems. Among the five compositions of TP conjugates, TP-2 system mediated a higher beta-galactosidase gene expression than PEI system in Jurkat cell which was known to express elevated numbers of transferrin receptors. From the results of the cell viability based on MTT assay, TP conjugates showed lower cytotoxicity compared with the PEI system. We expect that the TP conjugate can be used efficiently as a nonviral gene delivery vector.
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Kyung Man
authors.initials: KM
authors.lastname: Lee
authors.forename: In Sook
authors.initials: IS
authors.lastname: Kim
authors.forename: Yong Bok
authors.initials: YB
authors.lastname: Lee
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Shin
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
authors.forename: In Joon
authors.initials: IJ
authors.lastname: Oh
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel; D005562:Formazans; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D010316:Particle Size; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D011990:Receptors, Transferrin / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013778:Tetrazolium Salts; D014162:Transfection; D014168:Transferrin / Q000031:analogs & derivatives* / Q000235:genetics / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D005562:Formazans; D011990:Receptors, Transferrin; D013778:Tetrazolium Salts; D014168:Transferrin; C079782:MTT formazan; D011094:Polyethyleneimine