Tiopronin monolayer-protected silver nanoparticles modulate IL-6 secretion mediated by Toll-like receptor ligands
Tiopronin monolayer-protected silver nanoparticles modulate IL-6 secretion mediated by Toll-like receptor ligands
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DOI：
10.2217/17435889.3.5.627
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发表时间：
2008-10-01
期刊：
影响因子：
5.5
通讯作者：
Pozo, David
中科院分区：
文献类型：
--
作者：
Castillo, Paula M.;Herrera, Juan L.;Pozo, David
目的：可与多种分子和生物分子偶联的带帽银纳米粒子因其在生物医学中的潜在应用而引起人们的极大兴趣。然而，在主要的病原体相关分子模式受体，即Toll样受体(Toll-like Receptor，TLRs)结合后，还没有关于它们对关键的先天性免疫反应，如IL-6分泌的毒性或功能影响的数据。材料与方法：合成了粒径分布较窄(约5 nm)的N-(2-硫代丙酰基)甘氨酸(硫普罗宁)载银纳米粒(Ag@tiopronin)，并用透射电子显微镜、傅立叶变换红外光谱、拉曼光谱、核磁共振氢谱和全相关光谱对其进行了表征。用乳酸脱氢酶和3-[4，5-二甲基噻唑-2-基]-2，5-二苯基四氮唑比色法测定细胞毒性。采用双抗体夹心法测定IL-6水平。结果与讨论：银硫普罗宁纳米粒粒径分布窄(约5 nm)，在水环境中具有较高的溶解度和稳定性，在高达200 mU g/10(6)个细胞的浓度下，对线粒体功能和质膜完整性无细胞毒性。Ag@硫普罗宁纳米粒不是促炎药，但在共治疗实验中，它们显著地特异性地削弱TLR2、TLR2/6、TLR3或TLR9刺激介导的IL-6的分泌。然而，在预处理实验中，纳米粒增强了巨噬细胞对TLR2/1和TLR2/6特异性配体介导的炎症刺激的敏感性，而严重削弱了TLR3或TLR9配体激活的IL-6的分泌。结论：与未发现的银纳米粒相反，银@硫普罗宁纳米粒对巨噬细胞无细胞毒性。Ag@硫普罗宁纳米粒对TLR信号通路显示出高度特异性的差异性作用，本身无促炎作用。在使用银@硫普罗宁纳米颗粒的生物结合物用于未来的医疗应用时，必须考虑到这些影响。
Aims: Capped silver nanoparticles that can be coupled to a variety of molecules and biomolecules are of great interest owing to their potential applications in biomedicine. However, there are no data about their toxicity or functional effects on a key innate immune response, such as IL-6 secretion, after the engagement of the main group of pathogen-associated molecular patterns receptors, that is, the Toll-like receptors (TLRs). Materials & methods: N-(2-mercaptopropionyl)glycine (tiopronin)-capped silver (Ag@tiopronin) nanoparticles of a narrow sized distribution (similar to 5 nm) were synthesized and characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, Raman, H-1-NMR and total correlation spectroscopy. Cytotoxicity was determined by lactate deshidrogenase and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium assays in Raw 264.7 macrophages. IL-6 was measured by ELISA. Results & discussion: Ag@tiopronin nanoparticles have a narrow size distribution (approximate to 5 nm), high solubility and stability in aqueous environment with no cytotoxicity in terms of mitochondrial function or plasma-membrane integrity at concentrations as high as 200 mu g/10(6) cells. Ag@tiopronin nanoparticles were not proinflammatory agents, but remarkably they specifically impaired the IL-6 secretion mediated by TLR2, TLR2/6, TLR3 or TLR9 stimulation in co-treatment experiments. However, in pretreatment experiments, nanoparticles enhanced the susceptibility of macrophages to inflammatory stimulation mediated by TLR2/1 and TLR2/6 specific ligands while severely impairing the IL-6 secretion activated by the TLR3 or TLR9 ligands. Conclusions: Contrary to what is found for bare silver nanoparticles, Ag@tiopronin nanoparticles are noncytotoxic to macrophages. Ag@tiopronin nanoparticles showed differential effects on TLR signaling of a high degree of specificity, without proinflammatory effects by themselves. These effects have to be borne in mind when using bioconjugates of Ag@tiopronin nanoparticles for future medical applications.