Dual Enzyme-like Activities of Iron Oxide Nanoparticles and Their Implication for Diminishing Cytotoxicity
Dual Enzyme-like Activities of Iron Oxide Nanoparticles and Their Implication for Diminishing Cytotoxicity
复制标题
氧化铁纳米颗粒的双重酶样活性及其对减少细胞毒性的意义
DOI：
10.1021/nn300291r
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发表时间：
2012-05-01
期刊：
影响因子：
17.1
通讯作者：
Gu, Ning
中科院分区：
文献类型：
--
作者：
Chen, Zhongwen;Yin, Jun-Jie;Gu, Ning
氧化铁纳米颗粒（IONP）经常用于生物医学应用，但其潜在的毒性仍然是一个主要问题。虽然大多数生物安全研究都集中在接触纳米材料后的细胞反应上，但很少有报道分析纳米颗粒表面反应作为细胞毒性来源。在这里，我们报告说，不同的细胞内微环境中，IONP位于导致矛盾的结果，在他们的能力，产生自由基。我们首先验证了IONP的pH依赖性过氧化物酶样和过氧化氢酶样活性，并研究了它们如何在细胞内与过氧化氢（H2 O2）相互作用。结果表明，IONP对人脑胶质瘤U251细胞具有浓度依赖性的细胞毒作用，并能显著增强H2 O2对U251细胞的损伤。通过电子自旋共振实验，我们发现Fe 3 O 4和γ-Fe 2 O3纳米粒子在模拟酸性溶酶体条件下都能催化H2 O2产生羟基自由基，且相对效价Fe 3 O 4> γ-Fe 2 O3，这与它们的过氧化物酶样活性一致。然而，没有羟基自由基观察到在中性细胞质模拟条件与两种纳米粒子。相反，它们在这种条件下通过过氧化氢酶样活性直接将H2 O2分解为H2O和O-2。透射电子显微镜观察显示，IONP位于细胞内的溶酶体中，其酸性环境可能有助于羟基自由基的产生。这是第一个基于其酶样活性的细胞毒性研究。由于H2 O2在细胞中持续产生，我们的数据表明，IONP递送的溶酶体逃逸策略将是减少长期毒性潜力的有效方法。
Iron oxide nanoparticles (IONPs) are frequently used In biomedical applications, yet their toxic potential is still a major concern. While most studies of biosafety focus on cellular responses after exposure to nanomaterials, little is reported to analyze reactions on the surface of nanoparticles as a source of cytotoxicity. Here we report that different Intracellular microenvironment in which IONPs are located leads to contradictive outcomes in their abilities to produce free radicals. We first verified pH-dependent peroxidase-like and catalase-like activities of IONPs and investigated how they Interact with hydrogen peroxide (H2O2) within cells. Results showed that IONPs had a concentration-dependent cytotoxicity on human glioma U251 cells, and they could enhance H2O2-Induced cell damage dramatically. By conducting electron spin resonance spectroscopy experiments, we showed that both Fe3O4 and gamma-Fe2O3 nanoparticles could catalyze H2O2 to produce hydroxyl radicals in acidic lysosome mimic conditions, with relative potency Fe3O4 > gamma-Fe2O3, which was consistent with their peroxidase-like activities. However, no hydroxyl radicals were observed in neutral cytosol mimic conditions with both nanoparticles. Instead, they decomposed H2O2 into H2O and O-2 directly in this condition through catalase-like activities. Transmission electron micrographs revealed that IONPs located in lysosomes in cells, the acidic environment of which may contribute to hydroxyl radical production. This is the first study regarding cytotoxicity based on their enzyme-like activities. Since H2O2 is continuously produced in cells, our data indicate that lysosome-escaped strategy for IONP delivery would be an efficient way to diminish long-term toxic potential.