Investigation of polyethylenimine-grafted-triamcinolone acetonide as nucleus-targeting gene delivery systems

20Citations
Citations of this article
12Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

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.

Cite

CITATION STYLE

APA

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

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free