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具体来说,在二氧化硅纳米颗粒上形成的冠状物增强了转化生长因子 β1 在引发肺纤维化中的活性。

Specifically Formed Corona on Silica Nanoparticles Enhances Transforming Growth Factor β1 Activity in Triggering Lung Fibrosis.

机构信息

State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University , 163 Xianlin Avenue, Nanjing 210093, China.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Taipa, Macau SAR, China.

出版信息

ACS Nano. 2017 Feb 28;11(2):1659-1672. doi: 10.1021/acsnano.6b07461. Epub 2017 Jan 19.

Abstract

A corona is a layer of macromolecules formed on a nanoparticle surface in vivo. It can substantially change the biological identity of nanomaterials and possibly trigger adverse responses from the body tissues. Dissecting the role of the corona in the development of a particular disease may provide profound insights for understanding toxicity of nanomaterials in general. In our present study, we explored the capability of different silica nanoparticles (SiNPs) to induce silicosis in the mouse lung and analyzed the composition of coronas formed on these particles. We found that SiNPs of certain size and surface chemistry could specifically recruit transforming growth factor β1 (TGF-β1) into their corona, which subsequently induces the development of lung fibrosis. Once embedded into the corona on SiNPs, TGF-β1 was remarkably more stable than in its free form, and its fibrosis-triggering activity was significantly prolonged. Our study meaningfully demonstrates that a specific corona component on a certain nanoparticle could initiate a particular pathogenic process in a clinically relevant disease model. Our findings may shed light on the understanding of molecular mechanisms of human health risks correlated with exposure to small-scale substances.

摘要

在体内,纳米颗粒表面会形成一层大分子物质,即“冠”。它会极大地改变纳米材料的生物学特性,并可能引发机体组织的不良反应。剖析“冠”在特定疾病发展过程中的作用,可能会为深入了解纳米材料的毒性提供重要线索。在本研究中,我们探讨了不同二氧化硅纳米颗粒(SiNPs)在诱发小鼠肺部矽肺中的能力,并分析了这些颗粒形成的“冠”的组成。我们发现,特定大小和表面化学性质的 SiNPs 可特异性募集转化生长因子β1(TGF-β1)到“冠”中,进而诱发肺纤维化。一旦 TGF-β1 嵌入到 SiNPs 的“冠”中,其稳定性要比游离状态下显著增强,且引发纤维化的活性也明显延长。本研究意义重大,它表明在临床相关疾病模型中,特定纳米颗粒上的特定“冠”成分可引发特定的致病过程。我们的发现可能有助于阐明与暴露于小尺度物质相关的人类健康风险的分子机制。

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