Functional anti-inflammatory mesoporous silica nanoplatform for Synergistic and Targeted abdominal aortic aneurysm...

Abdominal aortic aneurysm (AAA) is a chronic inflammation-driven disease characterized by aortic wall destruction and expansion, leading to high morbidity and mortality. However, previous drug treatments for its common risk factors have not achieved favorable results, and the early prevention and treatment is still the main clinical dilemma. Anti-inflammation therapy is a promising therapeutical method targeting its pathogenesis mechanism, but it has not been explored in depth. Herein, interleukin-1 receptor antagonist-loaded manganese-doped mesoporous silica nanoparticles (IL-1Ra@MMSN) were designed and synthesized to target macrophage-mediated chronic aortic inflammation for AAA treatment. IL-1Ra@MMSN showed high IL-1Ra-loading efficiency, great stability and pH-responsive drug-releasing property. IL-1Ra@MMSN specially phagocytosed by macrophages can protect against oxidative stress injury and promoted the M2 polarization via transforming growth factor-β (TGF-β) signaling in vitro. Furthermore, IL-1Ra@MMSN exhibited good lesion targeting ability, hemocompatibility and biocompatibility in angiotensin II-induced murine AAA model. In vivo experiments also confirmed the excellent treatment efficacy in reducing AAA formation and progression via protecting aortic wall integrity and promoting anti-inflammatory microenvironment. Taken together, the current study demonstrated that IL-1Ra@MMSN is a promising nanoplatform for early intervention of AAA, which provides a novel treatment strategy based on anti-inflammatory immune regulation.