Size and surface modification of amorphous silica particles determine their effects on the activity of human CYP3A4 in vitro.
Size and surface modification of amorphous silica particles determine their effects on the activity of human CYP3A4 in vitro.
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DOI：
10.1186/1556-276x-9-651
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发表时间：
2014
影响因子：
--
通讯作者：
Tsutsumi Y
中科院分区：
文献类型：
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作者：
Imai S;Yoshioka Y;Morishita Y;Yoshida T;Uji M;Nagano K;Mukai Y;Kamada H;Tsunoda S;Higashisaka K;Tsutsumi Y
由于其有用的化学和物理特性，纳米材料在世界各地得到广泛使用-例如，作为食品和药品的添加剂-预计这种用途今后将更加普遍。因此，收集有关纳米材料对代谢酶影响的信息非常重要。在这里，我们研究了无定形二氧化硅颗粒与细胞色素P450 3A 4（CYP 3A 4）活性的不同大小和表面修饰的影响，通过两种不同的体外试验。直径为30和70 nm的二氧化硅纳米颗粒（分别为nSP 30和nSP 70）倾向于抑制人肝微粒体（HLM）中的CYP 3A 4活性，但这两种类型的纳米颗粒的抑制活性通过羧基修饰而降低。相反，胺修饰的nSP 70激活CYP 3A 4活性。在HepG 2细胞中，nSP 30比较大的二氧化硅颗粒更强烈地抑制CYP 3A 4活性。总之，这些结果表明二氧化硅颗粒的尺寸和表面特征决定了它们对CYP 3A 4活性的影响，并且通过改变它们的尺寸和表面特征，有可能开发出对代谢酶没有不良影响的二氧化硅颗粒。
Because of their useful chemical and physical properties, nanomaterials are widely used around the world - for example, as additives in food and medicines - and such uses are expected to become more prevalent in the future. Therefore, collecting information about the effects of nanomaterials on metabolic enzymes is important. Here, we examined the effects of amorphous silica particles with various sizes and surface modifications on cytochrome P450 3A4 (CYP3A4) activity by means of two different in vitro assays. Silica nanoparticles with diameters of 30 and 70 nm (nSP30 and nSP70, respectively) tended to inhibit CYP3A4 activity in human liver microsomes (HLMs), but the inhibitory activity of both types of nanoparticles was decreased by carboxyl modification. In contrast, amine-modified nSP70 activated CYP3A4 activity. In HepG2 cells, nSP30 inhibited CYP3A4 activity more strongly than the larger silica particles did. Taken together, these results suggest that the size and surface characteristics of the silica particles determined their effects on CYP3A4 activity and that it may be possible to develop silica particles that do not have undesirable effects on metabolic enzymes by altering their size and surface characteristics.