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表面修饰影响大鼠体内氧化铁磁性纳米颗粒的生物分布和毒性特征。

Surface modification affect the biodistribution and toxicity characteristics of iron oxide magnetic nanoparticles in rats.

作者信息

Yang Pengfei, Xu Hengyi, Zhang Zhihong, Yang Lin, Kuang Huijuan, Aguilar Zoraida P

机构信息

State Key Laboratory of Food Science and Technology, Nanchang University, 235 Nanjing East Road, Nanchang 330047, People's Republic of China.

Zystein, LLC, Fayetteville, AR 72704, USA.

出版信息

IET Nanobiotechnol. 2018 Aug;12(5):562-568. doi: 10.1049/iet-nbt.2017.0152.

Abstract

Various surface modifications of iron oxide magnetic nanoparticles (IOMNs) can improve their stability and long-term retention time , expanding applications of biomedical fields. However, whether the long-term retention of IOMNs coated with different surface modifications has toxic effects remains poorly understood. Here, the toxicity of IOMNs modified with polyethylene glycol (PEG), bovine serum albumin (BSA), and carboxyl group (COOH), forming PEG-IOMNs, BSA-IOMNs, and COOH-IOMNs, respectively, were evaluated in the rats. The high accumulation of PEG-IOMNs and COOH-IOMNs both in the liver and lung, and the high accumulation BSA-IOMNs in blood after 24 day recovery were observed by elemental content analysis. Except individual neutrophils in the local portal area, PEG-IOMNs can also induce cytoplasmic vacuolisation in partial liver cells by histopathological examination. Furthermore, the results of RT-qPCR showed that PEG-IOMNs, BSA-IOMNs, and COOH-IOMNs can change the transcript levels of most genes related to iron homeostasis, mitochondria apoptosis, inflammatory response, but <2-fold alteration. COOH-IOMNs seemed to induce normal cell apoptosis more easily than BSA-IOMNs and PEG-IOMNs. In conclusion, BSA-IOMNs had longer-term retention time in blood. IOMNs coated with PEG and BSA can still induce side effects on the liver.

摘要

氧化铁磁性纳米颗粒(IOMNs)的各种表面修饰可以提高其稳定性和长期保留时间,从而扩大其在生物医学领域的应用。然而,不同表面修饰的IOMNs长期保留是否具有毒性作用仍知之甚少。在此,分别用聚乙二醇(PEG)、牛血清白蛋白(BSA)和羧基(COOH)修饰形成PEG-IOMNs、BSA-IOMNs和COOH-IOMNs,并在大鼠中评估其毒性。通过元素含量分析观察到,在恢复24天后,PEG-IOMNs和COOH-IOMNs在肝脏和肺中均有高积累,而BSA-IOMNs在血液中有高积累。通过组织病理学检查发现,除局部门静脉区域的个别中性粒细胞外,PEG-IOMNs还可诱导部分肝细胞出现细胞质空泡化。此外,RT-qPCR结果表明,PEG-IOMNs、BSA-IOMNs和COOH-IOMNs可改变大多数与铁稳态、线粒体凋亡、炎症反应相关基因的转录水平,但变化倍数<2倍。COOH-IOMNs似乎比BSA-IOMNs和PEG-IOMNs更容易诱导正常细胞凋亡。总之,BSA-IOMNs在血液中的保留时间更长。PEG和BSA包被的IOMNs仍可对肝脏产生副作用。

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