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cRGD-platelet@MnO/MSN@PPARα/LXRα Nanoparticles Improve Atherosclerosis in Rats by Inhibiting Inflammation and Reducing Blood Lipid

炎症 体内 化学 泡沫电池 免疫印迹 血小板 ABCA1 药理学 血小板活化 胆固醇 受体 肝X受体 细胞凋亡 过氧化物酶体增殖物激活受体 内分泌学 内科学 脂蛋白 生物化学 医学 生物 核受体 生物技术 运输机 基因 转录因子
作者
Zheng Lv,Yupeng Zhang,Mengke Lu,Ziyi Wang,Xiaoyue Nong,Guoliang Wen,Wei Zhang
出处
期刊:Current Pharmaceutical Biotechnology [Bentham Science Publishers]
卷期号:26
标识
DOI:10.2174/0113892010314993240819065655
摘要

Objective: Atherosclerosis (AS) is an inflammatory disease of arterial intima driven by lipids. Liver X receptor alpha (LXRα) and peroxisome proliferator-activated receptor alpha (PPARα) agonists are limited in the treatment of AS due to their off-target effects and serious side effects. Therefore, this study was designed to construct a novel nanoparticle (NP) and evaluate its mechanism of action on inflammation inhibition and lipid reduction in AS. Methods: We synthesized cRGD-platelet@MnO/MSN@PPARα/LXRα NPs (cRGD-platelet- NPs) and confirmed their size, safety, and targeting ability through various tests, including dynamic light scattering and immunofluorescence. In vivo and in vitro experiments assessed cell proliferation, apoptosis, inflammation, and plaque formation. Finally, the NF-κB signaling pathway expression in rat aorta was determined using a western blot. Results: The synthesis of cRGD-platelet-NPs was successful; the particle size was approximately 150 nm, and the PDI was below 0.3. They could be successfully absorbed by cells, exhibiting high safety in vivo and in vitro. The cRGD-platelet-NPs successfully reduced plaque formation, improved lipid profiles by lowering LDL-cholesterol, total cholesterol, and triglycerides, and raised HDL-cholesterol levels. Additionally, they decreased inflammatory markers in the serum and aortic tissue, suggesting reduced inflammation. Immunohistochemistry and western blot analyses indicated that these NPs could not only promote M2 macrophage polarization but also suppress the NF-κB signaling pathway. Conclusion: The newly developed cRGD-platelet-NPs with high safety are a promising approach to AS treatment, which can regulate ABCA1, reduce the formation of AS plaques, and enhance cholesterol efflux. The mechanism may involve the suppression of the NF-κB signaling pathway.
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