Reduction of Reactive Oxygen Species Accumulation Using Gadolinium-Doped Ceria for the Alleviation of Atherosclerosis

Atherosclerosis is a common cardiovascular disease with increasing morbidity and mortality. The pathogenesis of atherosclerosis is strongly related to endothelial dysfunction, which is induced by severe oxidative stress damage derived from reactive oxygen species (ROS). Thus, ROS plays a critical role in the pathogenesis and progression of atherosclerosis. In this work, we demonstrated that the gadolinium doping of CeO₂ (Gd/CeO₂) nanozymes as effective ROS scavengers delivered high performance for antiatherosclerosis. It was found that the chemical doping of Gd promoted the surface proportion of Ce³⁺ in the nanozymes and thereby enhanced the overall ROS scavenging ability. In vitro and in vivo experiments unambiguously showed that the Gd/CeO₂ nanozymes efficiently scavenged harmful ROS at the cellular and histological levels. Further, Gd/CeO₂ nanozymes were demonstrated to significantly reduce vascular lesions by reducing lipid accumulation in macrophage and decreasing inflammatory factor levels, thereby inhibiting the exacerbation of atherosclerosis. Moreover, Gd/CeO₂ can serve as T₁-weighted magnetic resonance imaging contrast agents, which can generate sufficient contrast to distinguish the location of plaque during living imaging. Through those efforts, Gd/CeO₂ may serve as a potential diagnostic and treatment nanomedicine for the ROS-induced atherosclerosis.