Degradable co-delivery nanoplatforms for inflammation-targeted therapy against atherosclerosis AITranslate
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Highlights • This study develops an inflammation-targeted nanoplatform for the co-delivery of metal ions and anti-inflammatory drugs (IL-1Ra@Cu-MSNs) against atherosclerosis. • The impacts of copper ions on the phenotype and function of macrophages were illustrated for the first time. • IL-1Ra@Cu-MSNs significantly reduced arterial stenosis, plaque burden and macrophage infiltration due to the combination effects of IL-1Ra and copper ions. Atherosclerosis is characterized by chronic inflammation of the arterial wall. Activated macrophages play a significant role in the inflammatory process of atherosclerosis by secreting inflammatory factors such as interleukin-1 (IL-1) and interleukin-6 (IL-6). Among all the several methods to treat atherosclerosis, anti-inflammatory therapy with copper ions and IL-1 receptor antagonist (IL-1Ra) are the most promising approaches, but they are limited by side effects on liver damage and the short in vivo half-life of IL-1Ra, respectively. Herein, we developed an inflammation-targeted nanoplatform, i.e. IL-1Ra-loaded copper-doped mesoporous silica nanoparticles (IL-1Ra@Cu-MSNs), for co-delivery of IL-1Ra and copper ions. The nanoplatform showed outstanding drug-loading efficiency, sustained release property and biodegradability. Released copper ions specifically induced macrophage apoptosis by triggering ROS production. The loaded IL-1Ra conferred IL-1R-targeting and anti-inflammatory properties to the nanoplatform. In vivo study revealed that the IL-1Ra@Cu-MSNs significantly reduced arterial stenosis, plaque burden and macrophage infiltration due to the combined action of copper ions and IL-1Ra. Our work demonstrates that integration of targeted modulation of cellular function and inhibition of inflammation based on MSNs significantly alleviates arterial inflammation, which provides a novel strategy for the inflammation-targeted therapy against atherosclerosis. Graphical abstract Download : Download high-res image (133KB) Download : Download full-size image
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DOI：https://doi.org/10.1016/j.apmt.2021.101214
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Highlights • This study develops an inflammation-targeted nanoplatform for the co-delivery of metal ions and anti-inflammatory drugs (IL-1Ra@Cu-MSNs) against atherosclerosis. • The impacts of copper ions on the phenotype and function of macrophages were illustrated for the first time. • IL-1Ra@Cu-MSNs significantly reduced arterial stenosis, plaque burden and macrophage infiltration due to the combination effects of IL-1Ra and copper ions. Atherosclerosis is characterized by chronic inflammation of the arterial wall. Activated macrophages play a significant role in the inflammatory process of atherosclerosis by secreting inflammatory factors such as interleukin-1 (IL-1) and interleukin-6 (IL-6). Among all the several methods to treat atherosclerosis, anti-inflammatory therapy with copper ions and IL-1 receptor antagonist (IL-1Ra) are the most promising approaches, but they are limited by side effects on liver damage and the short in vivo half-life of IL-1Ra, respectively. Herein, we developed an inflammation-targeted nanoplatform, i.e. IL-1Ra-loaded copper-doped mesoporous silica nanoparticles (IL-1Ra@Cu-MSNs), for co-delivery of IL-1Ra and copper ions. The nanoplatform showed outstanding drug-loading efficiency, sustained release property and biodegradability. Released copper ions specifically induced macrophage apoptosis by triggering ROS production. The loaded IL-1Ra conferred IL-1R-targeting and anti-inflammatory properties to the nanoplatform. In vivo study revealed that the IL-1Ra@Cu-MSNs significantly reduced arterial stenosis, plaque burden and macrophage infiltration due to the combined action of copper ions and IL-1Ra. Our work demonstrates that integration of targeted modulation of cellular function and inhibition of inflammation based on MSNs significantly alleviates arterial inflammation, which provides a novel strategy for the inflammation-targeted therapy against atherosclerosis. Graphical abstract Download : Download high-res image (133KB) Download : Download full-size image
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| GB/T 7714-2015 | [1] Zhaoyu Wu, Zhijue Xu, Hongji Pu, et al. Applied Materials Today, 2021(25). DOI:10.1016/j.apmt.2021.101214. |
| MLA | [1] Zhaoyu Wu, et al., Applied Materials Today, no. 25, 2021, https://doi.org/10.1016/j.apmt.2021.101214. |
| APA | [1] Zhaoyu Wu, Zhijue Xu, Hongji Pu, Weimin Li, Junchao Liu, Zhen Zhao, Xinwu Lu, Kaili Lin, & Bo Li. (2021). Applied Materials Today(25). https://doi.org/10.1016/j.apmt.2021.101214 |
| IEEE | [1] Zhaoyu Wu, Zhijue Xu, Hongji Pu, Weimin Li, Junchao Liu, Zhen Zhao, Xinwu Lu, Kaili Lin, and Bo Li, Applied Materials Today, no. 25, 2021, doi: 10.1016/j.apmt.2021.101214. keywords: {Interleukin1 receptor antagonist;Copperdopped mesoporous silica nanoparticles;Macrophages;Atherosclerosis;Inflammation} |