Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), a life-threatening disease, is typically induced by uncontrolled inflammatory responses and excessive production of reactive oxygen species (ROS). Astaxanthin (Ast) is known for its powerful natural antioxidant properties, showcasing excellent antioxidant, anti-inflammatory, and immunomodulatory effects. However, its poor water solubility and bioavailability significantly limit its efficacy. Taking inspiration from biomimetic biology, this study developed a nasal drug delivery system comprising macrophage membrane (Mϕ)-encapsulated Ast-loaded nanoparticles (Mϕ@Ast-NPs) for the treatment of ALI. Mϕ@Ast-NPs retain the original homing properties of Mϕ, enabling targeted delivery to inflamed lungs and enhancing the anti-inflammatory effects of Astaxanthin (Ast). In vitro and in vivo, Mϕ@Ast-NPs demonstrated excellent biocompatibility and safety, as evidenced by no hemolysis of red blood cells and no significant toxic effects on cells and major organs. To determine the inflammation-targeting of Mϕ@Ast-NPs, both healthy and ALI mice were intranasally administered with Mϕ@Ast-NPs, the results demonstrated that highly targeting to inflamed lungs and endothelia, while with minimal accumulation in healthy lungs and endothelia. Mϕ@Ast-NPs effectively inhibited ROS production, enhanced Nrf2 expression and nucleus translocation, and reduced the levels of pro-inflammatory factors such as IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) in LPS-induced RAW264.7 cells and ALI mice. Our study provided a safe and effective nasal delivery platform for pulmonary diseases, and this biomimetic nano-formulation of Ast could be as functional foods in the future.

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.

An oral colon-targeted drug delivery system holds great potential in preventing systemic toxicity and preserving the therapeutic benefits of ulcerative colitis (UC) treatment. In this study, we developed a negatively charged PLGA-PEG nanoparticle system for encapsulating naringin (Nar). Additionally, chitosan and mannose were coated on the surface of these nanoparticles to enhance their mucosal adsorption and macrophage targeting abilities. The resulting nanoparticles, termed MC@Nar-NPs, exhibited excellent resistance against decomposition in the strong acidic gastrointestinal environment and specifically accumulated at inflammatory sites. Upon payload release, MC@Nar-NPs demonstrated remarkable efficacy in alleviating colon inflammation as evidenced by reduced levels of pro-inflammatory cytokines in both blood and colon tissues, as well as the scavenging of reactive oxygen species (ROS) in the colon. This oral nanoparticle delivery system represents a novel approach to treating UC by utilizing Chinese herbal ingredient-based oral delivery and provides a theoretical foundation for local and precise intervention in specific UC treatment.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common causes of respiratory failure in critically ill patients. There is still a lack of definitive and effective treatment options, and the mortality rate remains as high as 30% to 40%. Effective therapeutics for ALI/ARDS are greatly hindered by the side effects resulting from inefficient delivery to the disease lesions and off-targeting biodistribution of drugs. Macrophages play an integral role in maintaining the steady state of the immune system and are involved in inflammation processes. Thus, nanodrug to accurately target macrophages have the potential to transform disease treatment. Here, we developed an mannosylated drug delivery system to target and deliver celastrol (Cel) to the alveolar macrophages for enhanced alleviating the cytokines in LPS-induce ALI mice. In vitro data demonstrated that the as-synthesized Man@Cel-NPs significantly improved the targeting of Cel into the inflammatory macrophages via mannose receptor-mediated phagocytosis. In vivo experiments further showed that intratracheal delivery of Man@Cel-NPs can improve the dysregulation of inflammatory response in LPS-induced mice by inhibiting the release of inflammatory cytokines and increasing autophagy and decreasing apoptosis in lungs. This work provides a potential NP platform for the locally tracheal delivery of herbal ingredients and exhibits promising clinical potential in the treatment of numerous respiratory diseases, including ALI/ARDS.

The incidence of ulcerative colitis (UC) is rapidly rising worldwide. Oral drug delivery system is a promising approach for treating UC, but it often fails to accumulate to the inflammatory lesions, thus, it is impressive to develop a colon-targeted oral delivery system for preventing systemic toxicity and maintaining UC therapeutics. Here, a negative-charged PLGA nanoparticle system was designed to encapsulate celastrol (Cel), and then chitosan and mannose were coated on the surface of the nanoparticles (MC@Cel-NPs) to endow these nanoparticles with the mucosal adsorption and macrophage targeting abilities. MC@Cel-NPs demonstrate excellent resist decomposition ability against the strong acidic gastrointestinal environment, and accumulates in the specific inflammatory sites through the affinity of electrostatic reaction. After releasing the payload, MC@Cel-NPs could remarkably alleviate the colon inflammation, which was evidenced by the decrease in pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in both blood and colon sections, and scavenging reactive oxygen species (ROS) in colon cells, including macrophage, neutrophil, T cell, and B cell. This nanoparticle system provided a new approach for treating UC through a Chinese herbal ingredient-related oral delivery manner.

Abstract Background: Cytokine storm or cytokine release syndrome (CRS), mainly caused by the bacteria, viruses, etc., is life-threatening systemic inflammatory syndrome. CRS in the lung can lead to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in a very short time, and it is the main reason for patients with mild symptoms transferring to severe disease even death. Thus, effectively controlling CRS is essential in the prevention and treatment of infectious pneumonia. Methods: The naringin nanoparticles (Nar-NPs) were prepared by emulsification-and-evaporation method, and then the mesenchymal stem cell membranes were extracted and coated onto the surface of Nar-NPs by hand extrusion through nano-porous membranes to obtain cell membrane (CM) cloaked CM@Nar-NPs. The biocompatibility, inflammation-targeting, antioxidant capacity and anti-inflammatory efficiency were determined both in vitro and in vivo. Results The as-synthesized biomimetic platform (CM@Nar-NPs) showed highly efficient targeting and Nar delivery to the macrophages and alveolar epithelial cells as demonstrated by fluorescent imaging and flow cytometry analyses. The lung inflammation-targeting and accumulation of CM@Nar-NPs were also confirmed by IVIS imaging in septic mice. In LPS-induced sepsis mouse model, CM@Nar-NPs showed efficient therapeutic efficacy, as evidenced by improved survival rate, decreased pulmonary permeability and cytokine release, and the organ damage protection. Additionally, CM@Nar-NPs exhibited excellent antioxidant capacity, as evidenced by ROS scavenging in inflamed RAW264.7 cells and in the lung and liver of septic mice. To further determine the protective mechanism of CM@Nar-NPs, infiltrated macrophages in the lung were isolated and analyzed. CM@Nar-NPs increased the expression of M2 marker (CD206), and decreased the expression of M1 marker (F4/80) in septic mice, suggesting that Nar-modulated macrophages polarizing towards M2 subtype might contribute to their anti-inflammation effects. Conclusion The as-synthesized biomimetic platform (CM@Nar-NPs) can be employed to targeted delivery and improve the therapeutic efficacy of active ingredients from herbal medicine in the treatment of inflammatory diseases. This nanoplatform shows potential prospects for pneumonia-targeted delivery in clinics.

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.