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TIMP-2 gene transfer by positively charged PEG-lated monosized polycationic carrier to smooth muscle cells

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Abstract

Remodeling of the extracellular matrix resulting from increased secretion of metalloproteinase enzymes is implicated in restenosis following balloon angioplasty. Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases play an essential role in both normal and pathological extracellular matrix degradation. Tissue inhibitor of matrix metalloproteinase-2 is the most extensively studied tissue inhibitor of metalloproteinases in myocardial tissue in animal models and clinical examples of cardiac disease; therefore it is selected for this study. Gene transfer of tissue inhibitor of matrix metalloproteinase-2 may have a therapeutic potential by inhibition of matrix metalloproteinase activity. We have used PEG-lated nanoparticles poly(St/PEG-EEM/DMAPM) which were synthesized previously in our laboratory. The nanoparticles, with an average size of 77.6 ± 2.05 nm with a zeta potential of +64. 4 ± 1.14 mV and 201.9 ± 1.83 nm with +54.2 ± 0.77 mV were used in the transfection studies. Zeta Potential values and size of polyplex were appropriate for an effective transfection. TIMP-2 expression was detected by western blotting. Increased protein level in smooth muscle cells according to non-transfected smooth muscle cells confirms the successful delivery and expression of the tissue inhibitor of matrix metalloproteinase-2 gene with the non-viral vector transfection approach.

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Acknowledgments

This study was supported by the Turkish Scientific and Technological Council (Turkish Scientific and Technological Research Council, TÜBITAK; Project No. 104S334). Erhan Pişkin was also supported by the Turkish Academy of Sciences (TÜBA) as a full member.

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Authors and Affiliations

  1. Advanced Technology Education, Research and Application Center, Mersin University, 33343, Mersin, Turkey

    Nelisa Laçin

  2. Enzyme and Fermentation Technology Laboratory, Genetic Engineering and Biotechnology Institute, TUBITAK MAM, 41470, Gebze, Kocaeli, Turkey

    Güldem Utkan

  3. Chemical Engineering Department and Bioengineering Division, Hacettepe University, 06800, Ankara, Turkey

    Tülin Kutsal

  4. Chemical Engineering Department and Bioengineering Division and Center for Bioengineering—Biyomedtek, Hacettepe University, Ankara, Turkey

    Erhan Pişkin

  5. Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, 06800, Bilkent, Ankara, Turkey

    Bala Gür Dedeoğlu & Işık G. Yuluğ

Authors
  1. Nelisa Laçin
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  2. Güldem Utkan
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  3. Tülin Kutsal
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  4. Bala Gür Dedeoğlu
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  5. Işık G. Yuluğ
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  6. Erhan Pişkin
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Correspondence to Nelisa Laçin.

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Laçin, N., Utkan, G., Kutsal, T. et al. TIMP-2 gene transfer by positively charged PEG-lated monosized polycationic carrier to smooth muscle cells. J Nanopart Res 14, 694 (2012). https://doi.org/10.1007/s11051-011-0694-3

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  • DOI: https://doi.org/10.1007/s11051-011-0694-3

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