The effects of size and surface modification of amorphous silica particles on biodistribution and liver metabolism in mice
The effects of size and surface modification of amorphous silica particles on biodistribution and liver metabolism in mice
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DOI：
10.1088/0957-4484/26/17/175101
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发表时间：
2015-04
期刊：
影响因子：
3.5
通讯作者：
Xiaoyan Lu;C. Ji;Tingting Jin;Xiaohui Fan
中科院分区：
文献类型：
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作者：
Xiaoyan Lu;C. Ji;Tingting Jin;Xiaohui Fan
工程纳米颗粒具有非传统特性，是生物医学应用的有前途的平台。由于它们可能与多种生物分子相互作用，因此了解工程纳米粒子的物理化学性质对生物系统的影响至关重要。在这项研究中，通过小鼠模型中的一系列一般毒理学评估和代谢组学分析，确定了单独或组合无定形二氧化硅颗粒 (SP) 的粒径和表面改性对生物反应的影响。我们的结果表明，氨基或羧基表面修饰减轻了平面 SP 的肝毒性。经氨基表面修饰的 30 nm SP 被发现是相同剂量下所有表面修饰 SP 处理中毒性最强的 SP。当治疗剂量增加时，具有氨基或羧基表面修饰的亚微米级SP也会引起肝毒性。生物分布研究表明，无论表面修饰如何，70 nm SP 主要积累在肝脏和脾脏中。有趣的是，这两个器官表现出不同的吸收趋势。此外，代谢组学研究表明，表面修饰对肝脏代谢的影响比粒径更重要。
Engineered nanoparticles, with unconventional properties, are promising platforms for biomedical applications. Since they may interact with a wide variety of biomolecules, it is critical to understand the impact of the physicochemical properties of engineered nanoparticles on biological systems. In this study, the effects of particle size and surface modification alone or in combination of amorphous silica particles (SPs) on biological responses were determined using a suite of general toxicological assessments and metabonomics analysis in mice model. Our results suggested that amino or carboxyl surface modification mitigated the liver toxicity of plain-surface SPs. 30 nm SPs with amino surface modification were found to be the most toxic SPs among all the surface-modified SP treatments at the same dosage. When treatment dose was increased, submicro-sized SPs with amino or carboxyl surface modification also induced liver toxicity. Biodistribution studies suggested that 70 nm SPs were mainly accumulated in liver and spleen regardless of surface modifications. Interestingly, these two organs exhibited different uptake trends. Furthermore, metabonomics studies indicated that surface modification plays a more dominant role to affect the liver metabolism than particle size.