D-Mannose-Modified M2 Macrophage Membrane-Derived Decoy Nanovesicles for Synergistic Immunotherapy of Asthma

Eosinophilic asthma is a chronic inflammatory disease driven by Type 2 immune cells and cytokines. While cytokine-based immunotherapies have shown promising efficacy in asthma treatment, current approaches often fail to simultaneously target multiple cytokines. In this study, we present nanodecoys derived from the cellular membranes of M2 macrophages, which exhibit a high density of cytokine receptors, enabling efficient sequestration of multiple Type 2 cytokines. This mechanism significantly alleviates OVA-induced eosinophilic asthma inflammation in mice. To enhance therapeutic efficacy, D-mannose glycans, a potential immunoregulatory molecule for asthma, were modified onto the surface of the nanovesicles. This modification facilitates the phagocytic clearance of absorbed cytokines by targeting the mannose receptor (CD206). Consequently, the mannose-modified nanovesicles exhibit synergistic immunosuppressive effects on asthmatic inflammation by inhibiting M2 macrophage polarization, CD4⁺ T cell Th2 polarization, and eosinophil activation, as revealed by single-cell RNA sequencing and <i>in vitro</i> analyses. In summary, this study presents a safe and effective nanotechnology-based immunotherapy for asthma and potentially other Type 2 inflammatory diseases.