Functionalization of liposomes with ApoE-derived peptides affects cellular uptake and drug transport to atherosclerotic plaque

Author:

chen ling1,zhang tingjun1,Rong Cai2,xu zhengming3,tang xiaoxue3,Hu Houxiang4

Affiliation:

1. Jinan University

2. Chinese Academy of Sciences

3. North Sichuan Medical College

4. Academician Workstation, Affiliated Hospital of North Sichuan Medical College

Abstract

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.

Publisher

Research Square Platform LLC

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