期刊
POLYMER
卷 52, 期 2, 页码 339-346出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.polymer.2010.10.066
关键词
Dendrimer; 1,2-Diaminoethane moiety; Endosomal escape
资金
- Seoul National University (SNU)
- National Research Foundation of Korea (NRF) [2010-0007118]
- Ministry of Education, Science and Technology [M10534030004-09N3403-00410, 2009-0093632]
- National Research Foundation of Korea [2010-0007118] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
We synthesized a polyamidoamine (PAMAM) dendrimer with a 1,2-diaminoethane surface by an amidation reaction of PAMAM (G3.5) with diethylenetriamine (DET; PAM-DET). By titration and a lactate dehydrogenase (LDH) assay, we showed that PAM-DET has excellent buffering capacity and pH-dependent membrane destabilizing activity during the acidification process from pH 7.4 to pH 5.5. Further, through transfection experiments with various PAMAM derivatives that have different surface amines, we showed that the high transfection efficiency of PAM-DET was due to the introduction of a 1,2-diaminoethane moiety. Even though the intracellular uptake of PAM-DET was not significantly different from that of PAMAM, its transfection efficiency was highly dependent upon the presence of nigericin-an inhibitor of endosomal acidification-which verified that the increased transfection efficiency by PAM-DET originated from the facilitation of endosomal escape during endosome acidification. DNA-delivery efficiency can be greatly enhanced by this simple modification and small change to the surface amine structure. (C) 2010 Elsevier Ltd. All rights reserved.
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