Intratracheal Administration of Stem Cell Membrane-Cloaked Naringin-Loaded Biomimetic Nanoparticles Promotes Resolution of Acute Lung Injury.

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.