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Hyperbranched–dendrimer architectural copolymer gene delivery using hyperbranched PEI conjugated to poly(propyleneimine) dendrimers: synthesis, characterization, and evaluation of transfection efficiency

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Abstract

The applications of dendrimer-based vectors seem to be promising in non-viral gene delivery because of their potential for addressing the problems with viral vectors. In this study, generation 3 poly(propyleneimine) (G3-PPI) dendrimers with 1, 4-diaminobutane as a core initiator was synthesized using a divergent growth approach. To increase the hydrophobicity and reduce toxicity, 10% of primary amines of G3-PPI dendrimers were replaced with bromoalkylcarboxylates with different chain lengths (6-bromohexanoic and 10-bromodecanoic). Then, to retain the overall buffering capacity and enhance transfection, the alkylcarboxylate–PPIs were conjugated to 10 kDa branched polyethylenimine (PEI). The results showed that the modified PPI was able to form complexes with the diameter of less than 60 nm with net-positive surface charge around 20 mV. No significant toxicity was observed in modified PPIs; however, the hexanoate conjugated PPI–PEI (PPI-HEX-10% PEI) and the decanoate conjugated PPI–PEI (PPI-DEC-10%-PEI) showed the best transfection efficiency in murine neuroblastoma (Neuro-2a) cell line, even PPI-HEX-10%-PEI showed transfection efficiency equal to standard PEI 25 kDa with reduced toxicity. This study suggested a new series of hyperbranched (PEI)–dendrimer (PPI) architectural copolymers as non-viral gene delivery vectors with high transfection efficiency and low toxicity.

A schematic representative of hyperbranched PEI conjugated to poly(propyleneimine) dendrimers

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Acknowledgements

This work was founded by the National Science Foundation (INSF) (Grant number 91002289). The financial support by Mashhad University of Medical Sciences is also acknowledged. This study was a part of the MSc thesis of S. J. Alavi.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

    Seyyed Jamal Alavi

  2. Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Leila Gholami

  3. Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, P.O. Box: 91775-1159, Mashhad, Iran

    Saeedeh Askarian, Mehdi Rezaee & Reza Kazemi Oskuee

  4. Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Majid Darroudi

  5. Department of Chemistry, University of Payam noor, Mashhad, Iran

    Abdolhossein Massoudi

  6. Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Reza Kazemi Oskuee

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  1. Seyyed Jamal Alavi
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  2. Leila Gholami
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  3. Saeedeh Askarian
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Correspondence to Reza Kazemi Oskuee.

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Alavi, S.J., Gholami, L., Askarian, S. et al. Hyperbranched–dendrimer architectural copolymer gene delivery using hyperbranched PEI conjugated to poly(propyleneimine) dendrimers: synthesis, characterization, and evaluation of transfection efficiency. J Nanopart Res 19, 49 (2017). https://doi.org/10.1007/s11051-017-3739-4

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