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

• Published in: Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology Vol. 14; no. 2; pp. 1 - 9
• Main Authors: Laçin, Nelisa, Utkan, Güldem, Kutsal, Tülin, Dedeoğlu, Bala Gür, Yuluğ, Işık G., Pişkin, Erhan
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.02.2012; Springer Nature B.V
• Subjects: Characterization and Evaluation of Materials; Chemistry and Materials Science; Enzymes; Genes; Inhibitors; Inorganic Chemistry; Lasers; Materials Science; Matrix metalloproteinases; Muscles; Nanoparticles; Nanostructure; Nanotechnology; Optical Devices; Optics; Photonics; Physical Chemistry; Research Paper; Zeta potential; Nanoparticles; SMC; Gene therapy; Nanomedicine; TIMP
• ISSN: 1388-0764; 1572-896X
• DOI: 10.1007/s11051-011-0694-3

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.