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腺病毒介导的基因递送中纳米金/氧化铁磁性纳米颗粒的直接细胞内吞作用

Direct cell entry of gold/iron-oxide magnetic nanoparticles in adenovirus mediated gene delivery.

作者信息

Kamei Kazumasa, Mukai Yohei, Kojima Hiroki, Yoshikawa Tomoaki, Yoshikawa Mai, Kiyohara George, Yamamoto Takao A, Yoshioka Yasuo, Okada Naoki, Seino Satoshi, Nakagawa Shinsaku

机构信息

Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.

出版信息

Biomaterials. 2009 Mar;30(9):1809-14. doi: 10.1016/j.biomaterials.2008.12.015. Epub 2009 Jan 10.

Abstract

Gold/iron-oxide MAgnetic Nanoparticles (GoldMAN) imparts useful magnetic properties to various biomolecules. Gold nanoparticles immobilized on the surface of magnetic nanoparticles allow for the conjugation of biomolecules via an Au-S bond. Here, we present a practical application by utilizing GoldMAN and a magnetic field to induce intracellular transduction. This method has great potential for application of the adenovirus gene delivery vector (Ad), widely used for in vitro/in vivo gene transfer, to Ad-resistant cells. We demonstrated that Ad was easily immobilized on GoldMAN and the Ad/GoldMAN complex was introduced into the cell by the magnetic field, which increased gene expression over 1000 times that of Ad alone. The GoldMAN penetrated the plasma membrane directly, independent of the cell-surface virus receptors and endocytosis pathway. This mechanism will contribute to improve the gene expression efficiency of Ad. This technology is a useful tool for extending Ad tropism and enhancing transduction efficiency. GoldMAN also makes possible the effective use of various biomolecules within the cell because of its interesting cell-entry mechanism.

摘要

金/氧化铁磁性纳米颗粒(GoldMAN)赋予各种生物分子有用的磁性。固定在磁性纳米颗粒表面的金纳米颗粒允许生物分子通过金-硫键进行共轭。在此,我们展示了利用GoldMAN和磁场诱导细胞内转导的实际应用。该方法对于广泛用于体外/体内基因转移的腺病毒基因递送载体(Ad)应用于Ad抗性细胞具有巨大潜力。我们证明Ad很容易固定在GoldMAN上,并且Ad/GoldMAN复合物通过磁场被引入细胞,这使得基因表达比单独的Ad增加了1000倍以上。GoldMAN直接穿透质膜,独立于细胞表面病毒受体和内吞途径。这种机制将有助于提高Ad的基因表达效率。该技术是扩展Ad嗜性和提高转导效率的有用工具。由于其有趣的细胞进入机制,GoldMAN还使细胞内各种生物分子的有效利用成为可能。

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