Exosome membrane-modified M2 macrophages targeted nanomedicine: Treatment for allergic asthma

Abstract

BackgroundsExosomes are naturally secreted nanovesicles that have emerged as a promising therapeutic nanodelivery platform due to their specific composition, biological properties, and stability. Modifying synthetic nanoparticles with the intrinsic hallmarks of exosome membrane to create exosome mimetics could lead to safe and efficient smart silencer delivery. ObjectivesThe study focuses on exploring the combination of polylactic-co-glycolic acid (PLGA)-based nanoparticles with naturally occurring exosome membrane from M2 macrophages to deliver a Dnmt3aos smart silencer to treat allergic asthma (AA) in mice. Materials and methodsExosome membrane of M2 macrophages and PLGA nanoparticles (PLGA NPs) wrapped with the smart silencer of Dnmt3aos (Dnmt3aossmart silencer) were first synthesized. The resulting exosome membrane coated PLGA@Dnmt3aossmart silencer (EM-PLGA@Dnmt3aossmart silencer) was administered intravenously into Der f1-induced asthma mice, which was followed by the investigation of therapeutic outcomes and the mechanism in vivo. ResultsSeven infusions of EM-PLGA@Dnmt3aossmart silencer ameliorated AA with a marked reduction of lung inflammation. After intravenous injection, the EM-PLGA@Dnmt3aossmart silencer was distributed in various organs, including the lungs, with retention over 48 h, and it targeted M2 macrophages. Moreover, the injections of EM-PLGA@Dnmt3aossmart silencer markedly decreased the proportion of M2 macrophages and inflammatory cytokines in the airway. More importantly, the EM-PLGA@Dnmt3aossmart silencer treatment did not obviously suppress the overall immune function of host. ConclusionTo our knowledge, this study provides the first experimental evidence of the ability of EM-PLGA@Dnmt3aossmart silencer to target M2 macrophages in the treatment of AA by combining exosome membrane and biomaterials, thus presenting a novel immunotherapy for the allergic disease.