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

Abstract

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. and 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 and . 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.

© 2024 Bentham Science Publishers
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2024-09-02
2024-11-23

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/content/journals/cpb/10.2174/0113892010314993240819065655
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cRGD-platelet@MnO/MSN@PPARα/LXRα Nanoparticles Improve Atherosclerosis in Rats by Inhibiting Inflammation and Reducing Blood Lipid
Bentham Science Publishers ; https://doi.org/10.2174/0113892010314993240819065655
/content/journals/cpb/10.2174/0113892010314993240819065655
/content/journals/cpb/10.2174/0113892010314993240819065655
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  • Article Type:     Research Article
Keywords: nanoparticle ; inflammation ; lipid metabolism ; atherosclerosis ; reducing blood lipid ; cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles

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