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二氧化硅纳米颗粒的特定表面修饰可减少炎性小体激活及所选炎症基因的体内表达。

Specific Surface Modifications of Silica Nanoparticles Diminish Inflammasome Activation and In Vivo Expression of Selected Inflammatory Genes.

作者信息

Marzaioli Viviana, Groß Christina J, Weichenmeier Ingrid, Schmidt-Weber Carsten B, Gutermuth Jan, Groß Olaf, Alessandrini Francesca

机构信息

Center of Allergy and Environment (ZAUM), Technical University and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.

Institute for Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany.

出版信息

Nanomaterials (Basel). 2017 Oct 30;7(11):355. doi: 10.3390/nano7110355.

DOI:10.3390/nano7110355
PMID:29084176
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5707572/
Abstract

Silica (SiO₂) nanoparticles (NPs) usage includes, but is not limited to, industrial and biomedical applications. Toxic effects of SiO₂ NPs have been explored either or , assessing different surface modifications to reduce their harmful effects. Here, murine bone marrow-derived dendritic (BMDC) and a mouse model of mild allergic inflammation were used to study inflammasome activation and lung inflammation. Our results showed that SiO₂ plain NPs induced NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome activation, increasing interleukin (IL)-1β release , and, to a lesser extent, . In addition, SiO₂ plain NPs triggered a pulmonary inflammatory milieu in both non-sensitized (NS) and sensitized (S) mice, by inducing the expression of key inflammatory cytokines and chemokines. Electron microscopy showed that SiO₂ NPs were mostly localized in alveolar macrophages, within vesicles and/or in phagolysosomes. Both the and the effects of SiO NPs were attenuated by coating NPs with phosphonate or amino groups, whereas PEGylation, although it mitigated inflammasome activation , was not a successful coating strategy . These findings highlight that multiple assays are required to determine the effect of surface modifications in limiting NPs inflammatory potential. Taken together, these data are obtained by comparing and effects of SiO₂ NPs suggest the use of amino and phosphonate coating of silica NPs for commercial purposes and targeted applications, as they significantly reduce their proinflammatory potential.

摘要

二氧化硅(SiO₂)纳米颗粒(NPs)的用途包括但不限于工业和生物医学应用。已经探索了SiO₂ NPs的毒性作用,评估了不同的表面修饰以降低其有害影响。在这里,使用小鼠骨髓来源的树突状细胞(BMDC)和轻度过敏性炎症小鼠模型来研究炎性小体激活和肺部炎症。我们的结果表明,普通SiO₂ NPs诱导含NACHT、LRR和PYD结构域的蛋白3(NLRP3)炎性小体激活,增加白细胞介素(IL)-1β释放,并且在较小程度上增加 。此外,普通SiO₂ NPs通过诱导关键炎性细胞因子和趋化因子的表达,在未致敏(NS)和致敏(S)小鼠中引发肺部炎症环境。电子显微镜显示,SiO₂ NPs大多定位于肺泡巨噬细胞内、囊泡中和/或吞噬溶酶体中。用膦酸酯或氨基包被NPs可减弱SiO NPs的 和 作用,而聚乙二醇化虽然减轻了炎性小体激活 ,但不是一种成功的包被策略 。这些发现突出表明,需要多种测定方法来确定表面修饰在限制NPs炎症潜能方面的作用。综上所述,通过比较SiO₂ NPs的 和 作用获得的数据表明,出于商业目的和靶向应用,使用氨基和膦酸酯包被的二氧化硅纳米颗粒,因为它们可显著降低其促炎潜能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee4/5707572/45c386f32044/nanomaterials-07-00355-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee4/5707572/c15e5472526f/nanomaterials-07-00355-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee4/5707572/2c008907b59c/nanomaterials-07-00355-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee4/5707572/45c386f32044/nanomaterials-07-00355-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee4/5707572/1274f4263554/nanomaterials-07-00355-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee4/5707572/75f6cebf052e/nanomaterials-07-00355-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee4/5707572/2a00bba283ef/nanomaterials-07-00355-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee4/5707572/159da16cd17e/nanomaterials-07-00355-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee4/5707572/4a63c92dd566/nanomaterials-07-00355-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee4/5707572/2c008907b59c/nanomaterials-07-00355-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ee4/5707572/45c386f32044/nanomaterials-07-00355-g008.jpg

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