A metal-organic framework-based immunomodulatory nanoplatform for anti-atherosclerosis treatment

Immunomodulatory therapy has become a promising method for the clinical treatment of many diseases. Recently, pilot studies revealed that immunomodulatory therapy exhibited good effects on the treatment of cardiovascular diseases, but many problems remain to be solved, such as useful platforms for drug co-delivery and combination therapies. In this study, we designed and constructed the multifunctional nanoparticle Rapa@UiO-66-NH-FAM-IL-1Ra (RUFI) for the treatment of atherosclerotic cardiovascular disease. This nanoplatform combined the advantages of metal-organic frameworks (MOFs) for drug co-delivery, rapamycin and IL1Ra for immunomodulation, IL-1Ra for cellular targeting, and 5-FAM for fluorescence imaging. RUFI exhibited good drug release of rapamycin and IL-1Ra and specific cytotoxicity for inflammatory macrophages in vitro. In an atherosclerotic model of diet-fed ApoE-/- mice, RUFI significantly targeted and reduced atherosclerosis plaques in coronary arteries, carotid arteries, and aortas. Mechanistic studies indicated that RUFI modulated macrophage phenotype, cytokine expression, and autophagy. This study demonstrated that combination therapy with rapamycin and IL-1Ra via MOF carriers enhanced the immunoregulatory effects against atherosclerosis. This drug codelivery system suggests that MOF carriers loaded with immunomodulators are promising treatments for atherosclerosis or other inflammatory diseases.

Automated summary

Immunomodulatory therapy has shown promise in treating cardiovascular diseases, but challenges remain in terms of drug co-delivery and combination therapies. This study developed a multifunctional nanoparticle (RUFI) for treating atherosclerotic cardiovascular disease, which successfully targeted and reduced plaques in mouse models. The study demonstrated the enhanced immunoregulatory effects of combining rapamycin and IL-1Ra through MOF carriers, suggesting potential treatments for atherosclerosis and other inflammatory diseases.