Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
ThioMatrix GmbH, Research Center Innsbruck, Trientlgasse 65, 6020 Innsbruck, Austria.
Nanomedicine (Lond). 2017 Nov;12(22):2713-2724. doi: 10.2217/nnm-2017-0115. Epub 2017 Sep 29.
Aim of the study was the development of ζ potential changing nanoparticles as gene delivery system for the cystic fibrosis transmembrane conductance regulator gene.
Chitosan and carboxymethyl cellulose were modified with phosphotyrosine, a substrate for the brush border enzyme alkaline phosphatase. With these synthesized derivatives, different nanoparticle formulations, including the cystic fibrosis transmembrane conductance regulator gene were prepared by ionic gelation.
A change from negative to positive ζ potential after enzymatic cleavage could be observed. Transfection studies with HEK-293 and Caco-2 cells showed transfection rates comparable to Lipofectamine 2000. Transfection efficiencies were significantly decreased when phosphate cleavage and thus ζ potential change was inhibited by phosphatase inhibitor.
The developed nanoparticles represent a promising gene delivery system.
本研究旨在开发 ζ 电位变化纳米粒作为囊性纤维化跨膜电导调节基因的基因传递系统。
壳聚糖和羧甲基纤维素用磷酸酪氨酸进行修饰，磷酸酪氨酸是刷状缘酶碱性磷酸酶的底物。利用这些合成的衍生物，通过离子凝胶化制备了不同的纳米粒制剂，包括囊性纤维化跨膜电导调节基因。
酶切后可以观察到 ζ 电位从负到正的变化。用 HEK-293 和 Caco-2 细胞进行的转染研究表明，转染率可与 Lipofectamine 2000 相媲美。当通过磷酸酶抑制剂抑制磷酸基团的切割和 ζ 电位的变化时，转染效率显著降低。
所开发的纳米粒代表了一种有前途的基因传递系统。
