CeO₂/Bovine Serum Albumin Nanoclusters with Robust Reactive Oxygen Species Scavenging and Improved Endothelial Dysfunction Abilities for the Treatment of Pulmonary Hypertension

Endothelial dysfunction is one of the main pathogenetic mechanisms of pulmonary hypertension (PH). In the pathological microenvironment, excess reactive oxygen species (ROS) further induce pulmonary microvascular endothelial cell (PMEC) dysfunction. Recently, there has been an extreme lack of drugs that specifically target and eliminate ROS within the microenvironment. Although some nanomaterials are known as effective ROS-scavenging agents and can further alleviate disease progression, few nanomaterials have been reported in the endothelial dysfunction of PH. Based on the above situation, we synthesized a kind of novel nanoclusters (cerium dioxide/bovine serum albumin, CeO2/BSA), which can not only effectively scavenge ROS but also inhibit hypoxia-induced PMEC overproliferation, migration, and apoptosis resistance. CeO2/BSA nanoclusters were proved to be enriched in the lung, which effectively relieved pulmonary vascular remodeling, reduced the pressure of the pulmonary artery, and finally significantly improved cardiac function. Through in-depth mechanism analysis, we found that CeO2/BSA nanoclusters may be involved in Th1 and Th2 differentiation pathways mainly by effectively scavenging high levels of ROS in the pulmonary artery. In addition, the good biocompatibility of CeO2/BSA nanoclusters increased the possibility of their clinical application in the treatment of PH. In conclusion, this work provides a novel and effective solution to improve the dilemma of the ROS target and elimination in the treatment of PH.