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超顺磁性氧化铁纳米颗粒的仿生修饰及体内安全性评估

Biomimetic Modification and In Vivo Safety Assessment of Superparamagnetic Iron Oxide Nanoparticles.

作者信息

Song Xinfeng, Gu Xiangling, Sun Hanwen, Fu Chunhua, Zhang Yancong, Dong Pingxuan

出版信息

J Nanosci Nanotechnol. 2016 Apr;16(4):4100-7. doi: 10.1166/jnn.2016.11640.

DOI:10.1166/jnn.2016.11640
PMID:27451771
Abstract

The efficacy of superparamagnetic iron oxide nanoparticles (SPIONs) for biomedical applications depends on the magnetic properties, long time stability in biological fluids, and specific targeting capacity. The properties of SPIONs were generally improved by surface modification, but common modification technologies were usually conducted with multi-steps under rigid conditions. In this work, a facile and simple approach to synthesize functionalized SPIONs contrast agents was set up. First of all, SPIONs were prepared by an improved ultrasonic co-precipitation method. Then the surfaces of these SPIONs were modified biomimeticly by dopamine (DA) with strong adhesion. At last, the c(RGDyK), a biomolecule with the capacity of specific targeting capacity towards liver tumor cells, were coupled with DA on SPIONs via Mannich reaction. Thus the novel magnetic composite nanoparticles (abbreviated as c(RGDyK)-PDA-SPIONs) were successfully prepared. The as-synthesized nanoparticles were characterized by scanning electron microscope (SEM), dynamic light scattering, magnetic hysteresis loop measuring instrument. As a result, that the c(RGDyK)-PDA-SPIONs had an average size of about 50 nm and uniform distribution, and had superparamagnetic properties, good water dispersion stability. The acute toxicity test of the assynthesized c(RGDyK)-PDA-SPIONs to mice was also investigated. It was observed that LD50 of c(RGDyK)-PDA-SPIONs was 4.38 g/kg, with a 95% confidence interval ranging from 3.49 g/kg to 5.87 g/kg. These results indicated the novel c(RGDyK)-PDA-SPIONs had excellent biocompatibility, which was endowed with a potential capacity to serve as MRI contrast agents in diagnosis and treatment of the liver tumor.

摘要

超顺磁性氧化铁纳米颗粒(SPIONs)在生物医学应用中的功效取决于其磁性、在生物流体中的长时间稳定性以及特异性靶向能力。SPIONs的性能通常通过表面修饰得到改善,但常见的修饰技术通常需要在严格条件下分多步进行。在本研究中,建立了一种简便的合成功能化SPIONs造影剂的方法。首先,通过改进的超声共沉淀法制备SPIONs。然后,用具有强粘附性的多巴胺(DA)对这些SPIONs的表面进行仿生修饰。最后,通过曼尼希反应将具有对肝肿瘤细胞特异性靶向能力的生物分子c(RGDyK)与SPIONs上的DA偶联。从而成功制备了新型磁性复合纳米颗粒(简称为c(RGDyK)-PDA-SPIONs)。通过扫描电子显微镜(SEM)、动态光散射、磁滞回线测量仪对合成的纳米颗粒进行了表征。结果表明,c(RGDyK)-PDA-SPIONs的平均粒径约为50 nm,分布均匀,具有超顺磁性,在水中具有良好的分散稳定性。还研究了合成的c(RGDyK)-PDA-SPIONs对小鼠的急性毒性试验。观察到c(RGDyK)-PDA-SPIONs的半数致死量(LD50)为4.38 g/kg,95%置信区间为3.49 g/kg至5.87 g/kg。这些结果表明新型c(RGDyK)-PDA-SPIONs具有优异的生物相容性,具有在肝肿瘤诊断和治疗中用作磁共振成像(MRI)造影剂的潜在能力。

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