Copper oxide nanoparticles disrupt lysosomal function and promote foam cell formation in RAW264.7 macrophages

Macrophage-derived foam cells are crucial in the development of atherosclerosis, a multifaceted and progressive disorder characterized by lipid and fibrous accumulation in major arteries. Copper oxide nanoparticles (CuONPs) have found widespread applications but their potential role in atherosclerosis remains understudied. In this study, we investigated the impact of CuONPs on foam cell formation in RAW264.7 macrophages. Our results showed that CuONPs, at concentrations as low as 10 microg/ml, significantly exacerbated foam cell formation induced by oxidized low-density lipoprotein (ox-LDL). Exposure to CuONPs stimulated LDL release and elevated the expression of NLRP3 inflammasome components, including NLRP3, Caspase-1, and IL-1β. Transmission electron microscopy (TEM) revealed accumulation of CuONPs within macrophage lysosomes, leading to disrupted lysosomal function. CuONPs-treated cells exhibited autophagosome accumulation due to impaired lysosomal degradation, as confirmed by Western blot analysis showing abnormal expression of LAMP-1 and LAMP-2 proteins. Flow cytometry analysis further demonstrated decreased lysosomal acidity in CuONPs-exposed cells. Our findings reveal a novel mechanism whereby CuONPs activate the inflammasome, disrupt lysosomal function, and hinder cholesterol efflux, thereby exacerbating the formation of macrophage-derived foam cells. These results highlight the potential risks of CuONPs exposure and provide important insights into the role of environmental particulate matter in the development of atherosclerosis.