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利用磁性纳米颗粒将基因高效安全地递送至人角膜内皮细胞

Efficient and safe gene delivery to human corneal endothelium using magnetic nanoparticles.

作者信息

Czugala Marta, Mykhaylyk Olga, Böhler Philip, Onderka Jasmine, Stork Björn, Wesselborg Sebastian, Kruse Friedrich E, Plank Christian, Singer Bernhard B, Fuchsluger Thomas A

机构信息

Department of Ophthalmology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Institute of Anatomy, University Duisburg-Essen, Essen, Germany.

出版信息

Nanomedicine (Lond). 2016 Jul;11(14):1787-800. doi: 10.2217/nnm-2016-0144. Epub 2016 Jul 7.

Abstract

AIM

To develop a safe and efficient method for targeted, anti-apoptotic gene therapy of corneal endothelial cells (CECs).

MATERIALS & METHODS: Magnetofection (MF), a combination of lipofection with magnetic nanoparticles (MNPs; PEI-Mag2, SO-Mag5, PalD1-Mag1), was tested in human CECs and in explanted human corneas. Effects on cell viability and function were investigated. Immunocompatibility was assessed in human peripheral blood mononuclear cells.

RESULTS

Silica iron-oxide MNPs (SO-Mag5) combined with X-tremeGENE-HP achieved high transfection efficiency in human CECs and explanted human corneas, without altering cell viability or function. Magnetofection caused no immunomodulatory effects in human peripheral blood mononuclear cells. Magnetofection with anti-apoptotic P35 gene effectively blocked apoptosis in CECs.

CONCLUSION

Magnetofection is a promising tool for gene therapy of corneal endothelial cells with potential for targeted on-site delivery.

摘要

目的

开发一种用于角膜内皮细胞(CEC)靶向抗凋亡基因治疗的安全有效方法。

材料与方法

磁转染(MF),即脂质体转染与磁性纳米颗粒(MNP;PEI-Mag2、SO-Mag5、PalD1-Mag1)相结合,在人角膜内皮细胞和离体人角膜中进行测试。研究其对细胞活力和功能的影响。在人外周血单核细胞中评估免疫相容性。

结果

二氧化硅氧化铁磁性纳米颗粒(SO-Mag5)与X-tremeGENE-HP相结合在人角膜内皮细胞和离体人角膜中实现了高转染效率,且未改变细胞活力或功能。磁转染在人外周血单核细胞中未引起免疫调节作用。用抗凋亡P35基因进行磁转染可有效阻断角膜内皮细胞的凋亡。

结论

磁转染是一种有前景的角膜内皮细胞基因治疗工具,具有靶向原位递送的潜力。

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