Functional Peptide Hydrogel for the Synergistic Treatment of Atherosclerosis Based on Macrophage Autophagy Induction and Anti-Inflammation

Excess lipid accumulation and the progressive aggravation of chronic inflammation are the main characteristics of atherosclerosis (AS). Inducing autophagy has been proven to improve abnormal lipid metabolism and limitedly reduce the inflammatory response of macrophages. However, when the accumulation of inflammation exceeds the regulatory range of autophagy, the autophagy will become unbalanced. Therefore, we designed a short peptide-based hydrogel containing nonsteroidal anti-inflammatory drugs, to load with Fe3O4 nanoparticles for the anti-inflammatory and pro-autophagy synergistic therapy of AS. Fe3O4 activates autophagy, leading to a decrease in the uptake of oxidized low-density lipoprotein, and an increase in cholesterol excretion. By combination with anti-inflammatory agents, the occurrence of foam cells was decreased, and the release of pro-inflammatory cytokines and the generation of reactive oxygen species (ROS) were suppressed. Particularly, with autophagy activation, the decrease of macrophage apoptosis and the increase of macrophage burial further favored the stability of atherosclerotic plates. This study concentrates on the utilization of Fe3O4 to stimulate autophagy in macrophages and explores the potential of combining it with an anti-inflammatory peptide hydrogel for synergistic therapy, offering innovative approaches for treating AS.