VCAM-1-targeted and PPARδ-agonist-loaded nanomicelles enhanced suppressing effects on apoptosis and migration of oxidized low-density lipoprotein-induced vascular smooth muscle cells

细胞凋亡 内吞作用 兴奋剂 化学 低密度脂蛋白 血管平滑肌 体外 受体 脂蛋白 流式细胞术 分子生物学 生物物理学 生物化学 内分泌学 生物 胆固醇 平滑肌
作者
Gang Wei,Liangang Hao,Xueli Li,Xu Wen,Fuxiang Liu,Qian Peng,Shoutian Lv
出处
期刊:Bioscience Reports [Portland Press]
卷期号:40 (5) 被引量:7
标识
DOI:10.1042/bsr20200559
摘要

Abstract Purpose: Nanomicelles (NMs) have been widely used for various biomedical applications due to its unique physiochemical properties. The present study aims to investigate the effects of vascular cell adhesion molecule-1 (VCAM-1)-targeted and peroxisome proliferator-activated receptor δ (PPARδ) agonist (GW0742)-loaded NMs on apoptosis and migration in oxidized low-density lipoprotein (ox-LDL)-induced human aortic vascular smooth muscle cells (HAVSMCs). 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 with 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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