Degradable co-delivery nanoplatforms for inflammation-targeted therapy against atherosclerosis
Zhaoyu Wu, Zhijue Xu, Hongji Pu, Weimin Li, Junchao Liu, Zhen Zhao, Xinwu Lu, Kaili Lin, Bo Li
Abstract
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 ([email protected]), 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 [email protected] 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.