Peptide-based lipid nanodiscs suppress eosinophil recruitment and chemotaxis

Apolipoprotein A-I (ApoA-I) mimetic peptides hold promise for treating inflammatory lung diseases, yet their impact on eosinophils, key mediators of asthma and allergic airway inflammation, remains underexplored. We prepared self-assembling synthetic high-density lipoprotein (sHDL) nanoparticles using the bihelical ApoA-I mimetic peptide 4F-P-4F and phospholipids via microfluidics, yielding stable, nanodisc-shaped structures, as confirmed by in vitro and in silico analyses. These sHDL nanoparticles potently inhibited eotaxin-induced eosinophil migration in vitro, an effect reversed by blocking HDL receptors SR-BI and ABCA1. Mechanistically, sHDL promoted cholesterol efflux, disrupted CCR3 internalization, and modulated ERK1/2, STAT1, and STAT3 signaling. In an IL-5 transgenic mouse model, sHDL significantly reduced eosinophil infiltration in bronchoalveolar lavage. These results show that sHDL nanoparticles suppress eosinophil migration through targeted receptor interactions and signaling modulation, providing a mechanistic basis for further drug development.