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Interleukin-12 plasmid DNA delivery using l-thyroxine-conjugated polyethylenimine nanocarriers

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Abstract

In this study, l-thyroxine was covalently grafted on 25 kDa branched polyethylenimine (PEI), and the ability of the nano-sized polyplexes for transferring plasmid encoding interleukin-12 (IL-12) gene was evaluated. As there are several problems in systemic administration of recombinant IL-12 protein, local expression of the plasmid encoding IL-12 gene inside the tumor tissue has been considered as an effective alternative approach. The l-thyroxine-conjugated PEI polyplexes were prepared using pUMVC3-hIL12 plasmid, and their transfection activity was determined in HepG2 human liver carcinoma and Neuro2A neuroblastoma cell lines. The polyplexes characterized in terms of DNA condensation ability, particle size, zeta potential, and buffering capacity as well as cytotoxicity and resistance to enzyme digestion. The results revealed that l-thyroxine conjugation of PEI increased gene transfer ability by up to two fold relative to unmodified 25 kDa PEI, the gold standard for non-viral gene delivery, with the highest increase occurring at degrees of conjugation around 10 %. pDNA condensation tests and dynamic light scattering measurements exhibited the ability of PEI conjugates to optimally condense the plasmid DNA into polyplexes in the size range around 200 nm. The modified polymers showed remarkable buffering capacity and protection against enzymatic degradation comparable to that of unmodified PEI. These results suggest that l-thyroxine conjugation of PEI is a simple modification strategy for future investigations aimed at developing a targeting gene vehicle.

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Acknowledgments

This study was funded by the Shiraz University of Medical Sciences Shiraz, Iran (Grant number: 91-01-36-4847). The financial support by the Iranian Nanotechnology Initiative Council (INIC) is gratefully acknowledged. The results presented in this paper were parts of thesis of Mahin Fadaei and Zahra Sabahi. We would like to thank Amir Zarrinhaghighi and Mr. Akbarizadeh for their helpful assistances.

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Authors and Affiliations

  1. Department of Pharmaceutical Biotechnology, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran

    Ali Dehshahri, Mahin Fadaei, Zahra Sabahi, Samira Hossaini Alhashemi & Erfaneh Mohazabieh

  2. Pharmaceutical Sciences Research Center, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Ali Dehshahri, Mahin Fadaei, Zahra Sabahi, Samira Hossaini Alhashemi & Erfaneh Mohazabieh

  3. Department of Medicinal Chemistry, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Hossein Sadeghpour

  4. Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Reza Kazemi Oskuee

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  1. Ali Dehshahri
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  2. Hossein Sadeghpour
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Correspondence to Ali Dehshahri.

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Dehshahri, A., Sadeghpour, H., Kazemi Oskuee, R. et al. Interleukin-12 plasmid DNA delivery using l-thyroxine-conjugated polyethylenimine nanocarriers. J Nanopart Res 16, 2423 (2014). https://doi.org/10.1007/s11051-014-2423-1

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