Manipulation of macrophage polarization by peptide-coated gold nanoparticles and its protective effects on acute lung injury

Abstract

Background: Macrophage polarization and reprogramming in the lung play a critical role in the initiation, development and progression of acute lung injury (ALI). Regulating the activation and differentiation of pulmonary macrophages may provide a potential therapeutic strategy to treat ALI. We previously developed a novel class of antiinflammatory nanoparticles (P12) that can potently inhibit Toll-like receptor (TLR) signaling in macrophages. These bioactive nanodevices were made of gold nanoparticles (GNPs) coated with hexapeptides to not only ensure their physiological stability but also enable GNPs with TLR inhibitory activity.Results: In this study, using a lipopolysaccharide (LPS) induced ALI mouse model, we showed that P12 was able to alleviate lung inflammation and damage through reducing the infiltration of inflammatory cells and increasing the anti-inflammatory cytokine (IL-10) in the lung. These results prompted us to investigate possible macrophage polarization by P12. We first confirmed that P12 primarily targeted macrophages in the lung to exert anti-inflammatory activity. We then showed that P12 could drive the polarization of mouse bone marrow-derived macrophages (BMDMs) toward anti-inflammatory M2 phenotype. Interestingly, in the ALI mouse model, P12 was able to increase the alveolar M2 macrophages and reduce both the alveolar and interstitial M1 macrophages in the bronchoalveolar lavage fluid (BALF) and lung tissues. Conclusion:This study demonstrated that peptide-coated GNPs could induce M2 macrophage polarization in vitro and in vivo to effectively regulate lung inflammation, protect lung from injuries and promote inflammation resolution. The ability of regulating macrophage polarization together with TLR inhibition made such a bioactive nanodevice a new generation of potent therapeutics to treat ALI.

Induction of Innate Immune Memory by Engineered Nanoparticles in Monocytes/Macrophages: From Hypothesis to Reality

“…Many studies reveal an immunomodulatory role for NP (e.g., Au NPs, SiO 2 NP, functionalized polystyrene, and molybdenum disulfide quantum dots) that can drive macrophages polarization toward M1- or M2-like phenotypes ( 83 – 85 ). M1-like cells are classically activated inflammatory macrophages mainly involved in host defense to infections and tumors, while M2 defines alternatively activated macrophages mainly involved in type 2 inflammation, anti-inflammatory responses, wound-healing, tissue remodeling, and tumor growth ( 86 – 89 ).…”

Novel therapeutic approaches for treatment of COVID-19

“…Activation and polarization of macrophages play a major role in the initiation and intensity of inflammation, respectively, in ALI/ARDS. Peptide-coated gold nanoparticles could alleviate lung inflammation through inducing M1-to-M2 macrophage phenotype transition and increasing the anti-inflammatory cytokine (IL-10) in the lung of acute lung injury (ALI) mice [71].…”

Neutrophils and Macrophages as Targets for Development of Nanotherapeutics in Inflammatory Diseases

“…This approach may tune the inhibition of TLR4. Another study revealed that nanohybrids induced the polarization of alveolar M2 macrophages, but reduced M1 macrophages in an acute lung injury model [ 133 ].…”