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  • Title: Synthesis and characterization of a novel arginine-grafted dendritic block copolymer for gene delivery and study of its cellular uptake pathway leading to transfection.
    Author: Kim TI, Baek JU, Yoon JK, Choi JS, Kim K, Park JS.
    Journal: Bioconjug Chem; 2007; 18(2):309-17. PubMed ID: 17315976.
    Abstract:
    We synthesized a novel arginine-grafted dendritic block copolymer, R-PAMAM-PEG-PAMAM-R G5 (PPP5-R) for gene delivery systems. Its Mw was measured as 2.74 x 104 Da by MALDI-TOF, and approximately 36 arginine residues are found to be grafted to the polymer by 1H NMR. PPP5-R was able to form polyplexes with plasmid DNA, the average size of which was about 200 nm. Positive zeta-potential values (+22 to +28 mV) of PPP5-R polyplex indicate the formation of positively charged stable polyplex particles and suggest that large dendritic blocks with high positive charge may not be fully shielded by PEG chains even after PEG-coated complex formation. PPP5-R polyplex shows enhanced water solubility due to the polymer's PEG core and also shows low cytotoxicity, representing the potential for in vivo application. We identified the greatly enhanced transfection efficiency of PPP5-R in comparison with that of native PPP5 on various cell lines. Moreover, in view of the result of various cellular uptake inhibitor treatments during a transfection step, the cellular uptake of PPP5-R polyplex leading to effective transfection is thought to be not dependent on one exclusive pathway and to have the possibility of multiple pathways (caveolae-, clathrin-, and macropinocytosis-mediated pathways), contrary to the caveolae-dependent uptake of the PPP5 polyplex lacking arginine residues.
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