Therapies for atherosclerotic cardiovascular disease should target early disease stages and specific vascular sites where disease occurs. Endothelial glycocalyx (GCX) degradation compromises endothelial barrier function and increases vascular permeability. This initiates pro-atherosclerotic lipids and inflammatory cells to penetrate vessel walls, and at the same time this can be leveraged for targeted drug delivery. In prior cell culture studies, GCX degradation significantly increased endothelial cell uptake of nanoparticle vehicles that are designed for drug delivery, compared to the effects of intact GCX. The present study assessed if the cell culture findings translate to selective nanoparticle uptake in animal vessels. In mice, the left carotid artery (LCA) was partially ligated to disturb blood flow, which induces GCX degradation, endothelial dysfunction, and atherosclerosis. After ligation, the LCA vessel wall exhibited a loss of continuity of the GCX layer on the intima. 10-nm gold nanospheres (GNS) coated with polyethylene glycol (PEG) were delivered intravenously. GCX degradation in the ligated LCA correlated to increased GNS infiltration of the ligated LCA wall. This suggests that GCX dysfunction, which coincides with atherosclerosis, can indeed be targeted for enhanced drug delivery, offering a new approach in cardiovascular disease therapy.

动脉粥样硬化性心血管疾病的治疗应针对疾病的早期阶段和发生疾病的特定血管部位。内皮糖萼 (GCX) 降解会损害内皮屏障功能并增加血管通透性。这会引发促动脉粥样硬化脂质和炎症细胞穿透血管壁，同时可用于靶向药物输送。在之前的细胞培养研究中，与完整 GCX 的效果相比，GCX 降解显着增加了内皮细胞对专为药物输送而设计的纳米颗粒载体的摄取。本研究评估了细胞培养结果是否转化为动物血管中纳米颗粒的选择性摄取。在小鼠中，部分结扎左颈动脉（LCA）以扰乱血流，从而诱导 GCX 降解、内皮功能障碍和动脉粥样硬化。结扎后，LCA 血管壁表现出内膜上 GCX 层连续性的丧失。静脉注射涂有聚乙二醇 (PEG) 的 10 nm 金纳米球 (GNS)。结扎 LCA 中的 GCX 降解与结扎 LCA 壁的 GNS 浸润增加相关。这表明与动脉粥样硬化同时存在的 GCX 功能障碍确实可以作为增强药物输送的目标，为心血管疾病治疗提供一种新方法。