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

Abstract

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 (Dnmt3aossmart silencer) were first synthesized. The resulting exosome membrane coated [email protected]smart silencer ([email protected]smart silencer) 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 [email protected]smart silencer ameliorated AA with a marked reduction of lung inflammation. After intravenous injection, the [email protected]smart silencer was distributed in various organs, including the lungs, with retention over 48 h, and it targeted M2 macrophages. Moreover, the injections of [email protected]smart silencer markedly decreased the proportion of M2 macrophages and inflammatory cytokines in the airway. More importantly, the [email protected]smart silencer 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 [email protected]smart 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.

Topics & Concepts