Reprogramming multi-immune homeostasis in atherosclerotic plaques via inorganic violet phosphorus nano-immunotherapy (PRJCA049451)
Atherosclerosis is a chronic inflammatory disease driven by immune cell interactions within plaques. Nanotherapeutics targeting immune regulation within plaques offer promising potential for atherosclerosis treatment. However, most nanotherapies target single immune subsets and rarely examine cross-cell anti-atherosclerotic mechanisms. Here we develop a biocompatible inorganic nanoparticle platform (VPNS@P) that efficiently accumulates in the immune microenvironment of atherosclerotic plaques, particularly in macrophages, monocytes and partly T/B cells, with minimal off-target uptake. Additionally, our findings indicate that the VPNS@P reduces plaque areas and substantially improves plaque stability in atherosclerotic mice with no side effects. Importantly, we unravel the mechanisms of VPNS@P in atherosclerosis through scRNA-seq and experimental verification, demonstrating that it modulates key immune cell populations within plaques, to suppress inflammation and enhance immunity. VPNS@P reshapes intercellular communication among immune cells within plaques, revealing therapeutic targets for atherosclerosis. This study reveals an immune-modulating nanotherapy for atherosclerosis, highlighting the potential in treating inflammatory diseases.