Exosomes 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.
The 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.
Exosome membrane of M2 macrophages and PLGA nanoparticles (PLGA NPs) wrapped with the smart silencer of Dnmt3aos (Dnmt3aos) were first synthesized. The resulting exosome membrane coated PLGA@Dnmt3aos (EM-PLGA@Dnmt3aos) was administered intravenously into Der f1-induced asthma mice, which was followed by the investigation of therapeutic outcomes and the mechanism in vivo.
Seven infusions of EM-PLGA@Dnmt3aos ameliorated AA with a marked reduction of lung inflammation. After intravenous injection, the EM-PLGA@Dnmt3aos was distributed in various organs, including the lungs, with retention over 48 h, and it targeted M2 macrophages. Moreover, the injections of EM-PLGA@Dnmt3aos markedly decreased the proportion of M2 macrophages and inflammatory cytokines in the airway. More importantly, the EM-PLGA@Dnmt3aos treatment did not obviously suppress the overall immune function of host.
To our knowledge, this study provides the first experimental evidence of the ability of EM-PLGA@Dnmt3aos to target M2 macrophages in the treatment of AA by combining exosome membrane and biomaterials, thus presenting a novel immunotherapy for the allergic disease.

Copyright © 2021. Published by Elsevier B.V.