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

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.

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