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用于医学应用的用葡聚糖或聚乙二醇功能化的氧化铁纳米颗粒的体外和体内实验:磁靶向

In vitro and in vivo experiments with iron oxide nanoparticles functionalized with DEXTRAN or polyethylene glycol for medical applications: magnetic targeting.

作者信息

Mojica Pisciotti M L, Lima E, Vasquez Mansilla M, Tognoli V E, Troiani H E, Pasa A A, Creczynski-Pasa T B, Silva A H, Gurman P, Colombo L, Goya G F, Lamagna A, Zysler R D

机构信息

Div. Resonancias Magnéticas, Centro Atómico Bariloche/CONICET, S. C. Bariloche, 8400, Argentina.

出版信息

J Biomed Mater Res B Appl Biomater. 2014 May;102(4):860-8. doi: 10.1002/jbm.b.33068. Epub 2014 Jan 23.

DOI:10.1002/jbm.b.33068
PMID:24458920
Abstract

In this research work, DEXTRAN- and polyethylene glycol (PEG)-coated iron-oxide superparamagnetic nanoparticles were synthetized and their cytotoxicity and biodistribution assessed. Well-crystalline hydrophobic Fe3 O4 SPIONs were formed by a thermal decomposition process with d = 18 nm and σ = 2 nm; finally, the character of SPIONs was changed to hydrophilic by a post-synthesis procedure with the functionalization of the SPIONs with PEG or DEXTRAN. The nanoparticles present high saturation magnetization and superparamagnetic behavior at room temperature, and the hydrodynamic diameters of DEXTRAN- and PEG-coated SPIONs were measured as 170 and 120 nm, respectively. PEG- and DEXTRAN-coated SPIONs have a Specific Power Absorption SPA of 320 and 400 W/g, respectively, in an ac magnetic field with amplitude of 13 kA/m and frequency of 256 kHz. In vitro studies using VERO and MDCK cell lineages were performed to study the cytotoxicity and cell uptake of the SPIONs. For both cell lineages, PEG- and DEXTRAN-coated nanoparticles presented high cell viability for concentrations as high as 200 μg/mL. In vivo studies were conducted using BALB/c mice inoculating the SPIONs intravenously and exposing them to the presence of an external magnet located over the tumour. It was observed that the amount of PEG-coated SPIONs in the tumor increased by up to 160% when using the external permanent magnetic as opposed to those animals that were not exposed to the external magnetic field.

摘要

在这项研究工作中,合成了葡聚糖和聚乙二醇(PEG)包覆的氧化铁超顺磁性纳米颗粒,并评估了它们的细胞毒性和生物分布。通过热分解过程形成了结晶良好的疏水性Fe3O4超顺磁性氧化铁纳米颗粒,其粒径d = 18 nm,标准差σ = 2 nm;最后,通过用PEG或葡聚糖对超顺磁性氧化铁纳米颗粒进行功能化的后合成程序,将其性质转变为亲水性。这些纳米颗粒在室温下具有高饱和磁化强度和超顺磁性行为,葡聚糖和PEG包覆的超顺磁性氧化铁纳米颗粒的流体动力学直径分别测量为170和120 nm。在振幅为13 kA/m、频率为256 kHz的交流磁场中,PEG和葡聚糖包覆的超顺磁性氧化铁纳米颗粒的比功率吸收(SPA)分别为320和400 W/g。使用VERO和MDCK细胞系进行了体外研究,以研究超顺磁性氧化铁纳米颗粒的细胞毒性和细胞摄取。对于这两种细胞系,PEG和葡聚糖包覆的纳米颗粒在浓度高达200 μg/mL时均表现出高细胞活力。使用BALB/c小鼠进行了体内研究,通过静脉注射超顺磁性氧化铁纳米颗粒,并将它们暴露于位于肿瘤上方的外部磁体存在的环境中。观察到,与未暴露于外部磁场的动物相比,使用外部永磁体时,肿瘤中PEG包覆的超顺磁性氧化铁纳米颗粒数量增加了高达160%。

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