Galactose-modified nanoparticles for delivery of microRNA to mitigate the progress of abdominal aortic aneurysms via regulating macrophage polarization

Abdominal aortic aneurysms (AAA) are chronic inflammation in nature and are closely related to macrophages. The purpose was to explore regulating macrophage polarization with target-macrophage nanoparticles impacting the development of AAA. Galactose-modified nanoparticles were prepared by self-assembly technology for delivering microRNA (miR)-223. In AngiotensinII-induced experimental AAA model, miR-223-loaded nanoparticles (MirNPs) or PBS was injected at day 7 before and after operation, respectively. Cultured cells and aortic specimen were collected to be analyzed with histology and biochemical examination. In vitro, miR-223 promoted bone marrow-derived macrophages (BMDMs) to polarize to M2. In experimental AAA model, MirNPs significantly decreased the AAA incidence and the ratio of M1 macrophages and production of related proinflammatory cytokines. Furthermore, MirNPs also reduced the expression of the NLRP3 inflammasome. Our findings suggested that miR-223-loaded nanoparticles targeting macrophage polarization may mitigate AAA progression via downregulating of NLRP3.