Background: Nuclear membrane is one of the main barriers in polymer mediated intracellular gene delivery. To improve the transgenic activity and safety of nonviral vector, triamcinolone acetonide (TA) as a nuclear localization signal was conjugated with different molecular weight polyethylenimine (PEI). Methods: Different molecular weight PEI [600, 1800, 25 000 (25k)] was conjugated with TA to synthesize PEI-TA by two-step reaction. Their physicochemical characteristics, in vitro cytotoxicity and transfection efficiency were evaluated. To investigate the difference of transfection efficiency of various molecular weight PEI-TA, their transfection mechanism was further investigated by confocal microscopy and competition assay. Transgenic expression in vivo was evaluated by injection into hepatic portal vein of mice. Results: All PEI-TA could form nanosize polyplexes with DNA and their physicochemical properties resemble each other. Their cytotoxicities were negligible compared to PEI 25k. The order of transfection efficiency was PEI 1800-TA > PEI 600-TA > PEI 25k-TA. A transfection mechanism study displayed that TA could inhibit considerably the transgenic activity of PEI 1800-TA and PEI 600-TA, but that of PEI 25k-TA was not inhibited. It was suggested that PEI 1800-TA and PEI 600-TA might translocate into the nucleus. Confocal microscopy investigation verified this suggestion. The data strongly suggested that the transfection efficiency of PEI 1800-TA in vivo was much higher than that of PEI 25k, which was consistent with the results obtained in vitro. Conclusions: Low molecular weight PEI-TA could translocate into the nucleus efficiently. PEI 1800-TA presented higher transgenic activity and it has a great potential for gene therapy as a nonviral carrier. Copyright © 2010 John Wiley & Sons, Ltd.
CITATION STYLE
Ma, K., Hu, M., Xie, M., Shen, H., Qiu, L., Fan, W., … Jin, Y. (2010). Investigation of polyethylenimine-grafted-triamcinolone acetonide as nucleus-targeting gene delivery systems. Journal of Gene Medicine, 12(8), 669–680. https://doi.org/10.1002/jgm.1485
Mendeley helps you to discover research relevant for your work.