Interleukin-10-alveolar macrophage cell membrane-coated nanoparticles alleviate airway inflammation and regulate Th17/regulatory T cell balance in a mouse model

Abstract

BackgroundAllergic airway disease (AAD) is a chronic disease characterized by airway inflammation, bronchoconstriction, and hyperresponsiveness. Although exogenous interleukin-10 (IL-10) alleviates allergic inflammation, it has a short half-life in vivo. Cell membrane-coated nanomaterials have been shown to protect therapeutic payloads and increase therapeutic efficacy.ObjectiveThis study was aimed at investigating the efficacy of a novel macrophage-based nanoparticle drug for the treatment of house dust mite (HDM)-induced allergic airway diseases.MethodsIL-10-poly (lactic-co-glycolic acid (PLGA) nanoparticles were encapsulated in alveolar macrophage cell membranes. An allergic airway disease mouse model was established by repeated inhalation of HDM extracts. The mice were treated with free IL-10, IL-10-PLGA nanoparticles (IL10-NP), or IL-10-alveolar macrophage cell membrane-coated nanoparticles (IL10-AMNP). The therapeutic effects were evaluated by measuring airway hyperresponsiveness, lung inflammation, cytokine levels, and regulatory T cells (Treg)- T-helper 17 (Th17) cell balance.ResultsCompared to free IL-10, IL10-AMNP significantly reduced airway hyperresponsiveness and T-helper 2 (Th2)/Th17 cytokines and inhibited neutrophilia and eosinophilia recruitment into the airways of HDM-induced mouse models. Additionally, the balance between Tregs and Th17 cells was significantly improved in groups treated with IL10-AMNP.ConclusionThis study demonstrated that PLGA nanoparticle cores coated with alveolar macrophage cell membranes can effectively deliver therapeutic cytokines to the lungs and improve the homeostatic balance between Tregs and Th17 cells. These findings suggest that macrophage-based nanoparticle drugs represent a promising approach for treating allergic airway diseases.

Allergen-specific immunotherapy with Der p 1/2 mRNA vaccines alleviates house dust mite-induced allergic airway inflammation in a mouse model

“…Cells in BALF were centrifuged and suspended in fluorescence activated cell sorting (FACS) buffer. Sigle-cell lungs, mLNs and spleens suspensions were prepared by using 100-µm cell strainers and suspending in complete IMDM (cIMDM, IMDM medium plus 10% FBS and 1% penicillin-streptomycin, all from Gibco) as previously described 49 . In briefly, left lungs were scissored and incubated in 200 U/ml collagenase D and 25 µug/ml DNase I (Sigma) at 37°C for 45 min before passing through the cell strainers and were subsequently lysed in ammonium chloride buffer (BD Biosciences, USA).…”

Mechanism of regulating macrophages/osteoclasts in attenuating wear particle-induced aseptic osteolysis

“…Macrophage membrane-coated nanoparticles have high targeted delivery efficiency and show good therapeutic effects on various inflammatory diseases, including wear particle-induced periprosthetic inflammation ( 88 , 169 ). Currently, there are many types of nanoparticles or drugs coated in macrophage membranes, for example, lactose-acid nanoparticles ( 170 ), liposomes ( 169 ), poly(lactic-co-glycolic acid) ( 88 ), nano-gemcitabine ( 171 ), magnetic photothermal nanocomplexes ( 172 ), poly lactic-co-glycolic acid nanoparticle vaccine carrying PilY1 Ep ( 173 ) and mesoporous silica nanoparticles ( 174 ), etc. Macrophage membrane-coated drugs can avoid being recognized and cleared by the immune system, thereby enhancing the stability of drug release ( 175 ).…”