PDF(Pubmed)
Abstract：
Cytokine storm and ROS overproduction in the lung always lead to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in a very short time. Effectively controlling cytokine storm release syndrome (CRS) and scavenging ROS are key to the prevention and treatment of ALI/ARDS. In this work, the naringin nanoparticles (Nar-NPs) were prepared by the emulsification and evaporation method; then, the mesenchymal stem cell membranes (CMs) were extracted and coated onto the surface of the Nar-NPs through the hand extrusion method to obtain the biomimetic CM@Nar-NPs. In vitro, the CM@Nar-NPs showed good dispersity, excellent biocompatibility, and biosafety. At the cellular level, the CM@Nar-NPs had excellent abilities to target inflamed macrophages and the capacity to scavenge ROS. In vivo imaging demonstrated that the CM@Nar-NPs could target and accumulate in the inflammatory lungs. In an ALI mouse model, intratracheal (i.t.) instillation of the CM@Nar-NPs significantly decreased the ROS level, inhibited the proinflammatory cytokines, and remarkably promoted the survival rate. Additionally, the CM@Nar-NPs increased the expression of M2 marker (CD206), and decreased the expression of M1 marker (F4/80) in septic mice, suggesting that the Nar-modulated macrophages polarized towards the M2 subtype. Collectively, this work proves that a mesenchymal stem cell membrane-based biomimetic nanoparticle delivery system could efficiently target lung inflammation via i.t. administration; the released payload inhibited the production of inflammatory cytokines and ROS, and the Nar-modulated macrophages polarized towards the M2 phenotype which might contribute to their anti-inflammation effects. This nano-system provides an excellent pneumonia-treated platform with satisfactory biosafety and has great potential to effectively deliver herbal medicine.
摘要：
肺中的细胞因子风暴和ROS过量产生总是在很短的时间内导致急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)。有效控制细胞因子风暴释放综合征(CRS)和清除ROS是ALI/ARDS防治的关键。在这项工作中,采用乳化蒸发法制备柚皮苷纳米颗粒(Nar-NPs),提取间充质干细胞膜（CM），并通过手工挤压法包被在Nar-NP表面，获得仿生CM@Nar-NP。体外，CM@Nar-NP表现出良好的分散性，优异的生物相容性，和生物安全。在细胞层面,CM@Nar-NP具有优异的靶向发炎巨噬细胞的能力和清除ROS的能力。体内成像表明，CM@Nar-NP可以靶向并积聚在炎性肺中。在ALI小鼠模型中，气管内（i.t.）滴注CM@Nar-NP显着降低了ROS水平，抑制促炎细胞因子，显著提高了生存率。此外,CM@Nar-NP增加了M2标志物(CD206)的表达，并降低了M1标记（F4/80）在脓毒症小鼠中的表达，表明Nar调节的巨噬细胞向M2亚型极化。总的来说，这项工作证明，基于间充质干细胞膜的仿生纳米颗粒递送系统可以通过i.t.给药有效地靶向肺部炎症；释放的有效载荷抑制炎症细胞因子和ROS的产生，和Nar调节的巨噬细胞向M2表型极化，这可能有助于它们的抗炎作用。这种纳米系统提供了出色的肺炎治疗平台，具有令人满意的生物安全性，并且具有有效提供草药的巨大潜力。
