Basophil membrane-coated nanoparticles for IgE neutralization and allergy treatment

Immunoglobulin E (IgE) is a key mediator of allergic diseases, and its dysregulation can trigger systemic anaphylaxis and even be fatal. Despite its clinical importance, therapeutic options for safe and effective IgE neutralization remain limited. Here, we developed basophil membrane-coated nanoparticles (BMNPs) as a biomimetic strategy to sequester IgE. BMNPs were engineered by cloaking poly (lactic-co-glycolic acid) (PLGA) cores with RBL-2H3 cell (basophilic leukemia cell line)-derived membranes, preserving surface proteins such as FcεRI. These nanoparticles displayed selective IgE binding, competitively preventing IgE from engaging FcεRI on mast cells and thereby inhibiting degranulation upon allergen exposure. This led to decreased histamine and β-hexosaminidase release, lower Th2 cytokine levels (IL-4, IL-13), and attenuated Ca 2+ signaling and ERK/p38 activation as downstream consequences of reduced degranulation. In murine models of passive cutaneous and active systemic anaphylaxis, intravenously administered BMNPs effectively reduced circulating IgE, reduced vascular hyperpermeability, suppressed mast cell degranulation, and limited inflammatory cell infiltration. Transcriptomic profiling further indicated that BMNP-mediated IgE neutralization attenuates Ca 2+ influx and downregulates NF-κB, MAPK, and other proinflammatory pathways as downstream consequences of reduced mast cell degranulation in allergic regions. Importantly, BMNPs demonstrated favorable in vivo biosafety. Together, these results establish BMNPs as a safe and effective nanoplatform for IgE neutralization and suppression of IgE-mediated allergic responses, offering a promising therapeutic strategy for allergic diseases.