VCAM-1-targeted and PPARdelta-agonist-loaded nano micelles enhanced suppressing effects on apoptosis and migration of oxidized low-density lipoprotein-induced vascular smooth muscle cells.
2020
PURPOSE: Nano micelles (NMs) have been widely used for various biomedical applications due to its unique physiochemical properties. This study aims to investigate the effects of vascular cell adhesion molecule-1 (VCAM-1)-targeted and peroxisome proliferator-activated receptor delta (PPARdelta) agonist (GW0742)-loaded NMs on apoptosis and migration in oxidized low-density lipoprotein (ox-LDL)-induced human aortic vascular smooth muscle cells (HAVSMCs). Patients and Methods: The GW0742-loaded NMs (M-GW) and VCAM-1-targeted NMs loaded with GW0742 (TM-GW) were prepared, and then the morphologies and the size distribution of M-GM and TM-GM were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. In vitro drug release assay of M-GM and TM-GM were performed as well. Next, HAVSMCs were cultured in medium containing ox-LDL to mimic atherosclerotic environment, and the effects of free GW0742, M-GM and TM-GM on endocytosis, cell migration and apoptosis, as well as the expression of VCAM-1, and proteins associated with migration and apoptosis were measured in HAVSMCs treated with ox-LDL. RESULTS: M-GM and TM-GM were successfully prepared. VCAM-1 was overexpressed in HAVSMCs treated with ox-LDL, and TM-GM had a strong targeting ability to HAVSMCs treated with ox-LDL compared to M-GM. In addition, compared with free GW0742, both M-GM and TM-GM significantly diminished cell apoptosis and migration in HAVSMCs treated with ox-LDL. CONCLUSIONS: TM-GM had a superior suppressing effect on apoptosis and migration of ox-LDL-induced HAVSMCs.
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