Atherosclerosis is a progressive inflammatory disease characterised by excessive lipid accumulation and inflammatory cell infiltration and is the basis of most cardiovascular diseases and peripheral arterial diseases. Therefore, an effectively targeted delivery system is urgently needed to deliver ferroptosis-specific inhibitors to the site of arterial plaque and the inflammatory microenvironment. Inspired by the fact that neutrophils can be recruited to arterial plaques under the action of adhesion molecules and chemokines, the authors developed a neutrophil membrane hybrid liposome nano-mimetic system (Ptdser-NM-Lipo/Fer-1) that delivers Ferrostatin-1 (Fer-1) to the atherosclerotic plaque effectively, which is composed of Fer-1-loaded Ptdser-modified liposomes core and neutrophils shell. Fer-1 was released at the AS plaque site to remove reactive oxygen species (ROS) and improve the inflammatory microenvironment. In vitro ROS clearance experiments have shown that 50 μmol/ml Fer-1 can significantly remove ROS produced by H2 O2 -induced MOVAS cells and Ptdser-NM-Lipo/Fer-1 revealed a 3-fold increase in the inhibition rate of ROS than free Fer-1 in induced-RAW264.7, demonstrating its superior ROS-cleaning effect. Based on the interaction of adhesion molecules, such as vascular cell adhesion molecule 1, ICAM-1, P-selectin, E-selectin, and chemokines released in the inflamed site, the aorta in NM-Lipo-treated mice displayed 1.3-fold greater radiant efficiency than platelet membrane-Lipo-treated mice. Meanwhile, due to the modification of the Ptdser, the aorta in Ptdser-NM-Lipo/Fer-1-treated mice exhibited the highest fluorescence intensity, demonstrating its excellent targeting ability for atherosclerosis. Therefore, we present a specific formulation for the treatment of atherosclerosis with the potential for novel therapeutic uses.

中文翻译：

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中性粒细胞膜仿生输送系统 (Ptdser-NM-Lipo/Fer-1) 设计用于靶向动脉粥样硬化治疗。

动脉粥样硬化是一种以脂质过度积累和炎性细胞浸润为特征的进行性炎症性疾病，是大多数心血管疾病和外周动脉疾病的基础。因此，迫切需要一种有效的靶向递送系统，将铁死亡特异性抑制剂递送至动脉斑块部位和炎症微环境。受中性粒细胞在粘附分子和趋化因子的作用下可以被募集到动脉斑块这一事实的启发，作者开发了一种中性粒细胞膜混合脂质体纳米模拟系统（Ptdser-NM-Lipo/Fer-1），该系统可传递 Ferrostatin-1（ Fer-1)有效地作用于动脉粥样硬化斑块，其由负载Fer-1的Ptdser修饰的脂质体核心和中性粒细胞外壳组成。Fer-1 在 AS 斑块部位释放，以去除活性氧 (ROS) 并改善炎症微环境。体外ROS清除实验表明，50 μmol/ml Fer-1可以显着清除H2 O2诱导的MOVAS细胞产生的ROS，Ptdser-NM-Lipo/Fer-1对ROS的抑制率比Ptdser-NM-Lipo/Fer-1提高了3倍。诱导-RAW264.7 中游离的 Fer-1，证明了其卓越的 ROS 清洁效果。基于血管细胞粘附分子 1、ICAM-1、P-选择素、E-选择素和发炎部位释放的趋化因子等粘附分子的相互作用，NM-Lipo 治疗小鼠的主动脉显示出 1.3 倍的增大辐射效率高于血小板膜脂质处理小鼠。同时，由于Ptdser的修改，Ptdser-NM-Lipo/Fer-1处理小鼠的主动脉表现出最高的荧光强度，证明其对动脉粥样硬化具有出色的靶向能力。因此，我们提出了一种治疗动脉粥样硬化的特定制剂，具有新的治疗用途的潜力。