| dc.description.abstract | Oligoarginine, R9, is investigated of its potential on oligodeoxynucleotide (ODN) delivery. Cysteine modified R9 (R9C) and polyethylenimine (PEI) were also co-administrated so that there were 6 different delivery modes in this study, including PEI/ODN, R9/ODN, R9C/ODN, PEI-R9C/ODN (conjugates), PEI10/R9/ODN, and PEI/R9C/ODN. These carriers were complexed with ODN in different N/P ratios. Zeta potentials of formed nanoparticles increased with increasing carrier molecules. In contrast, R9 can only adsorb onto ODN without nanoparticle formation, which resulted in reducing repulse forces and leading ODN aggregation. However, the formed particle-sizes in all groups were ranged between 0.3 to 10µm, which were suitable for macrophage uptake. About the encapsulation, all carriers effectively loaded ODN except R9, and the loading efficiency increased with increasing carriers. The fluorescent microscopy illustrated that that all groups can deliver ODN into cells except the R9/ODN group. The confocal microscopy results suggested that R9C involving carrier systems (R9C/ODN, PEI10/R9C/ODN, and PEI-R9/ODN) can even facilitate endosomal escape. The biocompatibility assay suggested all carriers did not elicit severe cytotoxicity. Finally, we applied these systems to deliver anti-TNF-α ODN to evaluate their gene silence efficiencies. The results indicated that R9C/ODN and PEI10/R9C/ODN can inhibit TNF-α expression through transmembrane pathway. In contrast, PEI/ODN and PEI10/R9C/ODN can be uptake through endocytosis. Because PEI10/R9C/ODN can deliver ODN by both direct penetration and endocytosis pathways, the period of gene silence can be elongated, which should be an optimal delivery mode for clinical application. | en_US |