Neutrophil membrane-coated melanin nanoplatform: Targeted delivery of rapamycin and synergistic treatment of atherosclerosis.

Chronic inflammation establishes a persistent pathogenic microenvironment within atherosclerotic plaques. Given the central role of neutrophils in atherogenesis and their inherent inflammatory tropism, we designed a biomimetic nanoplatform (NM@HMR) for atherosclerotic management. NM@HMR was constructed by coating rapamycin-loaded hydrophilic melanin nanoparticles (HMR) with a neutrophil membrane (NM). Melanin, a potent antioxidant, acts synergistically with rapamycin to inhibit the proliferation of inflammatory macrophages, thereby exerting anti-atherosclerotic efficacy. This design preserves the natural antigenic profile and biological functions of the source cells. Compared to uncoated controls, NM@HMR exhibited enhanced interaction with multiple cellular components within atherosclerotic plaques. In vitro experiments revealed that NM@HMR effectively scavenged a broad spectrum of reactive oxygen species (ROS), suppressed macrophage proliferation, and inhibited foam cell formation. Following an eight-week in vivo administration, NM@HMR treatment markedly reduced atherosclerotic plaque area and increased plaque stability, without inducing significant systemic toxicity. In conclusion, these findings demonstrate that the NM@HMR platform represents a promising, safe, and effective nanotherapeutic strategy for the atherosclerosis management.