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Basic amino acid-conjugated polyamidoamine dendrimers with enhanced gene transfection efficiency

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Abstract

In this study, we characterized the polyamidoamine (PAMAM) dendrimer derivatives conjugated with basic amino acids as effective nonviral vector systems for gene delivery. Using PAMAM dendrimer (generation 4) as a core polymer, we further synthesized PAMAM G4-Histidine-Lysine (PAMAM G4-H-K) and PAMAM G4-Histidine-Ornithine (PAMAM G4-H-O). Lysine and ornithine have cationic charged groups that can contribute to the condensation of DNA and interaction with cellular membranes. Histidine has an imidazole ring group that can induce a proton buffering effect. In this report, we performed experiment to evaluate the basic amino acid-PAMAM conjugates as efficient and safe gene carriers. The mean diameter and zeta potential value of the PAMAM conjugates/DNA complex were measured to be around 100 nm and 30 mV, respectively. It was observed that the PAMAM derivatives and plasmid DNA can form polyplexes at weight ratio 1.5 by agarose gel retardation and PicoGreen reagent assay. Furthermore, the PAMAM derivatives have shown high buffering capacity compared to the native PAMAM dendrimer. We performed the cytotoxicity and transfection assay in the HeLa, HepG2, HEK 293, and NIH3T3 cell lines. While the transfection efficiency was remarkable in all cell lines tested, the cytotoxicity level was very low. Based on these characteristics, it is suggested that the basic amino acid-conjugated PAMAM dendrimers could be utilized as promising gene delivery polymeric vectors for effective gene therapy.

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Authors and Affiliations

  1. Department of Biochemistry, Chungnam National University, Daejeon, 305-764, Korea

    Jung Hyun Park & Joon Sig Choi

  2. School of Chemistry and Molecular Engineering, Seoul National University, 599 Gwanangno, Gwanakgu, Seoul, 151-742, Korea

    Jong-Sang Park

Authors
  1. Jung Hyun Park
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  2. Jong-Sang Park
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  3. Joon Sig Choi
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Correspondence to Jong-Sang Park or Joon Sig Choi.

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Park, J.H., Park, JS. & Choi, J.S. Basic amino acid-conjugated polyamidoamine dendrimers with enhanced gene transfection efficiency. Macromol. Res. 22, 500–508 (2014). https://doi.org/10.1007/s13233-014-2073-2

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  • DOI: https://doi.org/10.1007/s13233-014-2073-2

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