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Enhanced Delivery of Plasmid Encoding Interleukin-12 Gene by Diethylene Triamine Penta-Acetic Acid (DTPA)-Conjugated PEI Nanoparticles

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Abstract

Recombinant therapeutic proteins have been considered as an efficient category of medications used for the treatment of various diseases. Despite their effectiveness, there are some reports on the systemic adverse effects of recombinant therapeutic proteins limiting their wide clinical applications. Among different cytokines used for cancer immunotherapy, interleukin-12 (IL-12) has shown great ability as a powerful antitumor and antiangiogenic agent. However, significant toxic reactions following the systemic administration of IL-12 have led researchers to seek for alternative approaches such as the delivery and local expression of the IL-12 gene inside the tumor tissues. In order to transfer the plasmid encoding IL-12 gene, the most extensively investigated polycationic polymer, polyethylenimine (PEI), was modified by diethylene triamine penta-acetic acid (DTPA) to modulate the hydrophobic-hydrophilic balance of the polymer as well as its toxicity. DTPA-conjugated PEI derivatives were able to form complexes in the size range around 100–180 nm with great condensation ability and protection of the plasmid against enzymatic degradation. The highest gene transfer ability was achieved by the DTPA-conjugated PEI at the conjugation degree of 0.1 % where the level of IL-12 production increased up to twofold compared with that of the unmodified PEI. Results of the present study demonstrated that modulation of the surface positive charge of PEI along with the improvement of the polymer hydrophobic balance could be considered as a successful strategy to develop safe and powerful nanocarriers.

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Acknowledgments

This study was funded by Shiraz University of Medical Sciences, Shiraz, Iran. The financial support by the Iranian Nanotechnology Initiative Council (INIC) is gratefully acknowledged. The results presented in this paper were parts of the Pharm.D. thesis of Maryam Keykhaee. We would like to thank Dr Shiva Hemmati and Dr. Samira Hossaini Alhashemi for their helpful assistances.

Funding

This study was funded by Shiraz University of Medical Sciences, Shiraz, Iran.

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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, Maryam Keykhaee, Bahman Khalvati & Fatemeh Sheikhsaran

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

    Ali Dehshahri

  3. Center for Nanotechnology in Drug Delivery, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Ali Dehshahri

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

    Hossein Sadeghpour

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  1. Ali Dehshahri
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  2. Hossein Sadeghpour
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  3. Maryam Keykhaee
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  4. Bahman Khalvati
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Correspondence to Ali Dehshahri.

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Dehshahri, A., Sadeghpour, H., Keykhaee, M. et al. Enhanced Delivery of Plasmid Encoding Interleukin-12 Gene by Diethylene Triamine Penta-Acetic Acid (DTPA)-Conjugated PEI Nanoparticles. Appl Biochem Biotechnol 179, 251–269 (2016). https://doi.org/10.1007/s12010-016-1991-1

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