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Int J Pharm. 2014 Jan 1;459(1-2):10-8. doi: 10.1016/j.ijpharm.2013.11.027. Epub 2013 Nov 23.

Gene delivery of PAMAM dendrimer conjugated with the nuclear localization signal peptide originated from fibroblast growth factor 3.

Author information

  • 1Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, Republic of Korea.
  • 2Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, Republic of Korea; Korea Basic Science Institute (KBSI), 169-148 Gwahangno (52 Yeoeun-Dong), Yuseong-Gu, Daejeon 305-333, Republic of Korea.
  • 3Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, Republic of Korea; Department of Biochemistry, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: joonsig@cnu.ac.kr.

Abstract

Polyamidoamine (PAMAM) is one of the widely employed non-viral vectors in gene therapy research, and shows excellent biocompatibility and relatively low cytotoxicity. However, it has poor transfection efficiency compared with that of polyethylenimine (PEI, 25 kDa). To enhance the gene expression efficiency, we introduced the RRRK peptide from mouse fibroblast growth factor 3 (FGF3) to PAMAM, which is a known nuclear localization signal (NLS). We synthesized PAMAM-KRRR and PAMAM-RRRK to verify the difference of the induced functional status from reversal of the N-terminus. PAMAM containing the FGF3 peptide showed a transfection efficiency corresponding to that of PEI in HEK293, and HeLa cells, and showed much higher gene expression capacity than that of PEI in NIH3T3 cells with relatively decreased cytotoxicity. These results imply that introduction of the FGF 3 peptide has the potential to provide a novel PAMAM-based vector by enhancing its gene expression efficiency.

Copyright © 2013 Elsevier B.V. All rights reserved.

KEYWORDS:

Cytotoxicity; Mouse fibroblast growth factor 3; Nuclear localization signal; Polyamidoamine dendrimer; Polyplex; Transfection

PMID:
24275448
[PubMed - in process]
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