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用于胶质瘤靶向给药的乳铁蛋白修饰的氧化石墨烯氧化铁纳米复合材料

Lactoferrin modified graphene oxide iron oxide nanocomposite for glioma-targeted drug delivery.

作者信息

Song Meng-Meng, Xu Huai-Liang, Liang Jun-Xing, Xiang Hui-Hui, Liu Rui, Shen Yu-Xian

机构信息

School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, 230032 Hefei, Anhui, PR China; Biopharmaceutical Institute, Anhui Medical University, 81 Meishan Road, 230032 Hefei, PR China.

The Sixth Element (Changzhou) Materials Technology Co., Ltd., Changzhou, 213000, Jiangsu, PR China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2017 Aug 1;77:904-911. doi: 10.1016/j.msec.2017.03.309. Epub 2017 Apr 1.

Abstract

Targeting delivery of drugs in a specific manner represents a potential powerful technology in gliomas. Herein, we prepared a multifunctional targeted delivery system based on graphene oxide (GO) that contains a molecular bio-targeting ligand and superparamagnetic iron oxide nanoparticles on the surface of GO for magnetic targeting. Superparamagnetic FeO nanoparticles was loaded on the surface of GO via chemical precipitation method to form GO@FeO nanocomposites. Lactoferrin (Lf), an iron-transporting serum glycoprotein that binds to receptors overexpressed at the surface of glioma cells and vascular endothelial cell of the blood brain barrier, was chosen as the targeted ligand to construct the targeted delivery system Lf@GO@FeO through EDC/NHS chemistry. With the confirmation of TEM, DLS and VSM, the resulting Lf@GO@FeO had a size distribution of 200-1000nm and exhibited a superparamagnetic behavior. The nano delivery system had a high loading capacity and exhibited a pH-dependent release behavior. Compared with free DOX and DOX@GO@FeO, Lf@GO@FeO@DOX displayed greater intracellular delivery efficiency and stronger cytotoxicity against C6 glioma cells. The results demonstrated the potential utility of Lf conjugated GO@FeO nanocomposites for therapeutic application in the treatment of gliomas.

摘要

以特定方式靶向递送药物是一种在胶质瘤治疗中具有潜在强大作用的技术。在此,我们制备了一种基于氧化石墨烯(GO)的多功能靶向递送系统,该系统在GO表面含有分子生物靶向配体和超顺磁性氧化铁纳米颗粒用于磁靶向。通过化学沉淀法将超顺磁性FeO纳米颗粒负载在GO表面以形成GO@FeO纳米复合材料。乳铁蛋白(Lf)是一种运输铁的血清糖蛋白,它能与胶质瘤细胞表面和血脑屏障血管内皮细胞上过表达的受体结合,被选为靶向配体,通过EDC/NHS化学方法构建靶向递送系统Lf@GO@FeO。经透射电子显微镜(TEM)、动态光散射(DLS)和振动样品磁强计(VSM)确认,所得的Lf@GO@FeO尺寸分布为200 - 1000nm,并表现出超顺磁性行为。该纳米递送系统具有高负载能力,并表现出pH依赖性释放行为。与游离阿霉素(DOX)和DOX@GO@FeO相比,Lf@GO@FeO@DOX对C6胶质瘤细胞表现出更高的细胞内递送效率和更强的细胞毒性。结果证明了Lf偶联的GO@FeO纳米复合材料在胶质瘤治疗中的潜在应用价值。

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