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N-己酰壳聚糖稳定的磁性纳米颗粒:增强腺病毒介导的基因在体外和体内的表达

N-hexanoyl chitosan-stabilized magnetic nanoparticles: enhancement of adenoviral-mediated gene expression both in vitro and in vivo.

作者信息

Bhattarai Shanta Raj, Kim Sun Young, Jang Kyu Yun, Lee Ki Chang, Yi Ho Keun, Lee Dae Yeol, Kim Hak Yong, Hwang Pyoung Han

机构信息

Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan, USA.

出版信息

Nanomedicine. 2008 Jun;4(2):146-54. doi: 10.1016/j.nano.2008.02.001. Epub 2008 Apr 18.

Abstract

We developed hexanoyl chloride-modified chitosan (Nac-6) stabilized iron oxide nanoparticles (Nac-6-IOPs) as magnetic nanoparticles for viral gene (Ad/LacZ) delivery via magnetofection. This vector, Nac-6-IOPs/Ad/LacZ, binds to K562 cells in the presence of external magnetic fields and results in enhanced expression of the transgene in those cells that do not exhibit the coxsackie-adenovirus receptor (CAR). Our results demonstrate that Nac-6-IOPs/Ad/LacZ is able to transduce K562 cells specifically with reduced infection of CAR- cells. The dramatic enhancement in intracellular trafficking of the adenovirus without genetically modified vesicles can lead to enhanced nuclear transfer, especially in CAR- cells. In vivo magnetofection results also clearly demonstrated that the present Nac-6-IOPs could be applied in other cell lines. Whether cells or organs, in the presence of magnetic fields Nac-6-IOPs/Ad/LacZ has high transduction efficiency. The newly formulated Nac-6-IOPs, introduced by magnetofection, provide a high-throughput gene screening both in vitro and in vivo.

摘要

我们开发了己酰氯修饰的壳聚糖(Nac-6)稳定的氧化铁纳米颗粒(Nac-6-IOPs)作为磁性纳米颗粒,用于通过磁转染递送病毒基因(Ad/LacZ)。这种载体Nac-6-IOPs/Ad/LacZ在外部磁场存在下与K562细胞结合,并导致在不表达柯萨奇腺病毒受体(CAR)的那些细胞中转基因表达增强。我们的结果表明,Nac-6-IOPs/Ad/LacZ能够特异性转导K562细胞,同时减少对CAR-细胞的感染。在没有基因修饰囊泡的情况下,腺病毒细胞内运输的显著增强可导致核转运增强,尤其是在CAR-细胞中。体内磁转染结果也清楚地表明,目前的Nac-6-IOPs可应用于其他细胞系。无论是细胞还是器官,在磁场存在下,Nac-6-IOPs/Ad/LacZ都具有高转导效率。通过磁转染引入的新配制的Nac-6-IOPs在体外和体内都提供了高通量基因筛选。

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