Omidi Yadollah, Barar Jaleh
Research Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Int J Toxicol. 2009 Mar-Apr;28(2):113-22. doi: 10.1177/1091581809335177.
Although nonviral dendrimeric nanostructures have been widely used as gene delivery systems, key questions about target cells responses to these nanostructures are yet to be answered. Here, we report the responsiveness of A431 and A549 cells upon treatment with polypropylenimine diaminobutane (DAB) dendrimers nanosystems. Complexation of DAB dendrimers with DNA reduced the zeta potential of nanostructures, but increased their size. Fluorescence microscopy revealed high transfection efficiency in both cell lines treated with DAB dendrimers with induced cytotoxicity evidenced by MTT assay. The A549 cells showed upregulation of epidermal growth factor receptor (EGFR) and its downstream signalling biomolecule Akt kinase upon treatment with DAB dendrimers, while no changes were observed in A431 cells. Based on our findings, the biological impacts of these nanosystems appeared to be cell dependent. Thus, the biological responses of target cells should be taken into account when these nanostructures are used as gene delivery system.
尽管非病毒树枝状纳米结构已被广泛用作基因递送系统，但关于靶细胞对这些纳米结构的反应的关键问题仍有待解答。在此，我们报告了用聚亚丙基亚胺二氨基丁烷（DAB）树枝状聚合物纳米系统处理后A431和A549细胞的反应情况。DAB树枝状聚合物与DNA复合降低了纳米结构的zeta电位，但增加了它们的尺寸。荧光显微镜显示，用DAB树枝状聚合物处理的两种细胞系中均有高转染效率，MTT分析证明存在诱导的细胞毒性。在用DAB树枝状聚合物处理后，A549细胞显示表皮生长因子受体（EGFR）及其下游信号生物分子Akt激酶上调，而在A431细胞中未观察到变化。基于我们的发现，这些纳米系统的生物学影响似乎取决于细胞。因此，当这些纳米结构用作基因递送系统时，应考虑靶细胞的生物学反应。
