Abstract
Purpose
Nanomedicine has gathered significant attention in atherosclerosis. However, there remains an apparent gap between laboratory discovery and clinical translation of nanomaterials. Therefore, we constructed a new nanomaterial that selected liposomes as drug-delivery carriers. and modified with Apolipoprotein E (ApoE) peptides which may alleviate atherosclerotic plaque to seek a novel idea about treatment of atherosclerosis .
Methods
We successfully constructed nanoparticles loaded with Atorvastatin and modified them with aE15A (ApoE peptide) (Lip@A@15A). In vitro, the study of cellular uptake of nanomaterials by macrophages was detected by Confocal laser scanning microscopy (CLSM), and concentrations of inflammatory factors were detected using Enzyme-linked Immunosorbent Assay. In vivo, ApoE-/- mice were used to construct atherosclerotic models that were treated with many reagents, including Lip@A@15A, in which the stability of atherosclerotic plaque in aortas and the macrophage-derived foam cells were observed by oil “O” and Masson staining.
Results
Lip@A@15A showed low toxicity in an in vitro cytotoxicity test and had the highest phagocytic efficiency by macrophages compared to liposomes and nanoparticles loaded with atorvastatin (Lip@A). Therefore, the function of lipid phagocytosis and the levels of IL-1βand TNF-αin macrophages treated with Lip@A@15A were the lowest compared with that of macrophages treated with the other three reagents (P<0.05). More importantly, Lip@A@15A may be localized in the aortic intima. Lip@A@15A markedly improved plaque stability and inhibited plaque rupture compared with mice treated with other reagents.
Conclusion
Relative to Lip@A, Lip@A@15A more significantly enhanced endocytosis by macrophages and impeded inflammatory factors from macrophages. In addition, it actively targeted atherosclerotic plaques and improved plaque stability.