Biosafety study and mechanism comparison on two types of silica with different nanostructures
Biosafety study and mechanism comparison on two types of silica with different nanostructures
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两种不同纳米结构二氧化硅的生物安全性研究及机理比较
DOI：
10.1039/c7tx00076f
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发表时间：
2017
影响因子：
2.1
通讯作者：
Wang Xueqing
中科院分区：
文献类型：
--
作者：
Zhang Yang;Chen Xianhui;Zhao Bo;Wu Hounan;Yuan Lan;Zhang Hua;Dai Wenbing;He Bing;Xing Gengmei;Zhang Qiang;Wang Xueqing
二氧化硅经常用于口服给药；然而，它的生物安全性，特别是它的纳米结构，还没有得到全面的研究。在此，比较了两种二氧化硅(A200，纳米或微米级团聚体；S350，带有纳米孔的微米级颗粒)的体外和体内生物安全性，并探讨了造成差异的可能原因。结果表明，A200和S350均可通过诱导细胞凋亡和改变细胞周期进程来抑制Caco-2细胞的生长。在大多数体外实验中，A200显示出比S350更强的影响。在昆明种小鼠的活体实验中，A200和S350都能改变实验条件下的血液成分，A200还能增加血浆中炎症因子的水平和CD4+淋巴细胞亚群的数量。A200和S350处理组均未观察到明显的器质性损伤。转运研究表明，A200和S350在体内外都不容易通过肠上皮屏障转运，但A200可以穿过淋巴相关上皮细胞并聚集在Peyer‘s补片中，这可能解释了A200诱导的免疫反应。A200的转运增加可能与其颗粒大小、分散状态和比表面积有关。综上所述，这些结果表明A200和S350表现出不同的生物安全性，这与它们不同的纳米结构有关。我们相信这项研究将为A200和S350在口服给药系统中的应用提供一些关于生物安全性的科学信息。
Silica is frequently used in oral drug delivery; however, its biosafety, particularly concerned with its nanostructure, has not been comprehensively studied yet. Here, thein vitroandin vivobiosafety of two types of silica (A200, nano-sized or micron-sized agglomerates; S350, micro-sized particles with nanopores) were compared and the possible reasons for the differences were explored. The results indicated that both A200 and S350 could inhibit the growth of Caco-2 cells by inducing apoptosis and changing the cell cycle progression. A200 showed a stronger influence than S350 in most of thein vitroexperiments. In thein vivostudy in KM mice, both A200 and S350 could change the blood constituents under the tested conditions; A200 also increased the levels of inflammatory factors in plasma and the numbers of CD4+ lymphocyte subsets. No obvious organic damage was observed in either the A200-treated or S350-treated groups. The transport study showed that neither A200 nor S350 were readily transported across the intestinal epithelial barrierin vitroandin vivo, but A200 could transport across the lymphatic-associated epithelium and accumulate in the Peyer's Patches, which might explain the A200-induced immune response. The increased transport of A200 might relate to its particle size, dispersion state and specific surface area. In conclusion, these results demonstrated that A200 and S350 exhibited diverse biosafety aspects, which correlated with their different nanostructures. We believe this study will provide some scientific information about the biosafety of A200 and S350 for their applications in oral drug delivery systems.