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.
ABSTRACT
Patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) are often septic and with poor prognosis, which leads to a high mortality rate of 25-40%. Despite the advances in medicine, there are no effective pharmacological therapies for ALI/ARDS due to the short systemic circulation and poor specificity in the lungs. To address this problem, we prepared TP-loaded nanoparticles (TP-NPs) through the emulsification-and-evaporation method, and then the platelet membrane vesicles were extracted and coated onto the surface of the NPs to constitute the biomimetic PM@TP-NPs. In a LPS-induced ALI mouse model, PM@TP-NPs showed good biocompatibility and biosafety, which was evidenced by no significant toxic effect on cell viability and no hemolysis of red blood cells. In ALI mice, the PM@TP-NPs showed favorable anti-inflammation and enhanced therapeutic activity of TPs compared to the free drug. Administration of PM@TP-NPs effectively inhibited lung vascular injury, evidenced by the decreased lung vascular permeability, reduced pro-inflammatory cytokine burden, evidenced by decreased inflammatory cell (macrophages, neutrophils, etc.) infiltration in the bronchoalveolar lavage fluid (BALF) and lung tissues, and inhibited the secretion of pro-inflammatory cytokines and NLRP3 inflammasome activation. ALI/ARDS is defined by damage to the alveolar epithelium and endothelium; thus, effective intervention targeting pulmonary vascular endothelial cells (VECs) is crucial for the treatment of respiratory diseases. For further determination of the targeting of PM cloaked NPs, healthy mice were also administered with the same NPs. Interestingly, the PM cloaked NPs only showed highly efficient targeting to the inflamed lungs and VECs, but no accumulation in healthy lungs and VECs. The data demonstrated that this biomimetic nanoplatform could be used as a potential strategy for personalized therapies in the treatment of inflammatory diseases, such as ALI/ARDS, and even COVID-19-associated pneumonia.
Subject(s)
Acute Lung Injury , COVID-19 , Nanoparticles , Respiratory Distress Syndrome , Mice , Animals , Lipopolysaccharides/pharmacology , Endothelial Cells , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Cytokines , Tea/adverse effects , Mice, Inbred C57BLABSTRACT
Acute lung injury (ALI) is an inflammatory response which causes serious damages to alveolar epithelia and vasculature, and it still remains high lethality and mortality with no effective treatment. Based on the inflammatory homing of platelets and cell membrane cloaking nanotechnology, in this study we developed a biomimetic anti-inflammation nanoparticle delivery system for ALI treatment. PM@Cur-RV NPs were designed by combining the poly (lactic-co-glycolic acid) nanoparticles (NPs) coated with platelet membrane vesicles (PM) for the purpose of highly targeting delivery of curcumin (Cur) and resveratrol (RV) to inflammatory lungs. PM@Cur-RV NPs showed good biocompatibility and biosafety both in vitro and in vivo. Accumulation of NPs into lung tract was observed after inhaled NPs. Remarkably, the inhalation of PM@Cur-RV NPs effectively inhibited lung vascular injury evidenced by the decreased lung vascular permeability, and the reduced proinflammatory cytokine burden in an ALI mouse model. The analysis of infiltrated macrophages in the lungs showed that the Cur-RV-modulated macrophage polarized towards M2 phenotype and the decreased histone lactylation might contribute to their anti-inflammation effects. Together, this work highlights the potential of inhalation of biomimetic nanoparticle delivery of curcumin and resveratrol for the treatment of pulmonary diseases.
ABSTRACT
Asthma is one of the most common chronic pulmonary disorders, affecting more than 330 million people worldwide. Unfortunately, there are still no specific treatments for asthma so far. Therefore, it is very important to develop effective therapeutics and medicines to deal with this intractable disease. Berberine (Ber) has fabulous anti-inflammatory and antibacterial effects, while its low water solubility and bioavailability greatly limit its curative efficiency. To improve the nasal mucosa absorption of poorly water-soluble drugs, such as Ber, we developed a platelet membrane- (PM-) coated nanoparticle (NP) system (PM@Ber-NPs) for targeted delivery of berberine to the inflammatory lungs. In vivo, PM@Ber-NPs exhibited enhanced targeting retention in the inflammatory lungs compared with free Ber. In a mouse model of house dust mite- (HDM-) induced asthma, PM@Ber-NPs markedly inhibited lung inflammation, as evident by reduced inflammatory cells and inflammatory cytokines in the lung compared with free Ber. Collectively, our study demonstrated the inhibitory actions of nasally delivered nanomedicines on HDM-induced asthma, primarily through regulating Th1/Th2 balance by enhancing IL-12 expression which could potentially reduce lung inflammation and allergic asthma.
