Modifying the Surface of Silica Nanoparticles with Amino or Carboxyl Groups Decreases Their Cytotoxicity to Parenchymal Hepatocytes.
Modifying the Surface of Silica Nanoparticles with Amino or Carboxyl Groups Decreases Their Cytotoxicity to Parenchymal Hepatocytes.
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DOI：
10.1248/bpb.b16-00917
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发表时间：
2017-05
影响因子：
2
通讯作者：
T. Nagano;K. Nagano;H. Nabeshi;Tokuyuki Yoshida;H. Kamada;S. Tsunoda;Jianqing Gao;K. Higashisaka;Y. Yoshioka;Y. Tsutsumi
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文献类型：
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作者：
T. Nagano;K. Nagano;H. Nabeshi;Tokuyuki Yoshida;H. Kamada;S. Tsunoda;Jianqing Gao;K. Higashisaka;Y. Yoshioka;Y. Tsutsumi
我们之前报道过，直径为 70 nm 的未修饰二氧化硅纳米粒子 (nSP70) 会引起小鼠肝损伤，而经过羧基或氨基修饰的 nSP70 则不会。此外，我们发现未修饰和修饰的 nSP70 均定位于库普弗细胞和实质肝细胞中。因此，我们评估了这些细胞群摄取 nSP70 对肝损伤的贡献。为此，我们用氯化钆 (III) 水合物 (GdCl3) 预处理小鼠，以防止库普弗细胞摄取 nSP70，随后给小鼠注射任一类型的 nSP70，然后评估血浆丙氨酸转氨酶 (ALT) 水平。在给予 GdCl3 的小鼠中，未修饰的 nSP70 增加了 ALT 水平。根据这些数据，我们假设在 GdCl3 处理的小鼠中，被阻止进入 Kupffer 细胞的未修饰的 nSP70 被分流到实质肝细胞，在那里它诱导细胞毒性并增加肝脏损伤。相比之下，GdCl3 预处理对注射表面修饰的 nSP70 的小鼠的 ALT 水平没有影响，这表明修饰的 nSP70 不会损害实质肝细胞，因此引起的肝损伤可以忽略不计。在细胞毒性分析中，暴露于表面修饰的 nSP70 时，实质肝细胞系的活力高于未修饰的 nSP70。这些发现表明，与未修饰的 nSP70 相比，表面修饰相关的肝损伤减少可归因于对实质肝细胞的细胞毒性降低。
We previously reported that unmodified silica nanoparticles with diameters of 70 nm (nSP70) induced liver damage in mice, whereas nSP70 modified with carboxyl or amino groups did not. In addition, we have found that both unmodified and modified nSP70s localize in both Kupffer cells and parenchymal hepatocytes. We therefore evaluated the contributions of nSP70 uptake by these cell populations to liver damage. To this end, we pretreated mice with gadolinium (III) chloride hydrate (GdCl3) to prevent nSP70 uptake by Kupffer cells, subsequently injected the mice with either type of nSP70, and then assessed plasma levels of alanine aminotransferase (ALT). In mice given GdCl3, unmodified nSP70 increased ALT levels. From these data, we hypothesized that in GdCl3-treated mice, the unmodified nSP70 that was prevented from entering Kupffer cells was shunted to parenchymal hepatocytes, where it induced cytotoxicity and increased liver damage. In contrast, GdCl3 pretreatment had no effect on ALT levels in mice injected with surface-modified nSP70s, suggesting that modified nSP70s spared parenchymal hepatocytes and thus induced negligible liver damage. In cytotoxicity analyses, the viability of a parenchymal hepatocyte line was greater when exposed to surface-modified nSP70s than to unmodified nSP70s. These findings imply that the decreased liver damage associated with surface-modified compared with unmodified nSP70 is attributable to decreased cytotoxicity to parenchymal hepatocytes.