Background: Pulmonary microvascular endothelial cells (PMECs) dysfunction, the important pathophysiological feature of pulmonary arterial hypertension (PAH), can be caused by many harmful stimulating factors including increase in the level of reactive oxygen species (ROS).

This pathological features of offer tremendous promise for nanotechnology.

Aim: Prepare a nano antioxidant for eliminating ROS.

Methods: An ultra-small CeO2@BSA nanocluster was synthesized by protein bionic method as an antioxidant. The ROS (H2O2, ·O2- and ·OH) scavenging ability of CeO2@BSA nanocluster was determined using kits. The effects of CeO2@BSA on cell proliferation, apoptosis, and migration were assessed using CCK-8 assay, flow cytometry, and scratch test, respectively. Subsequently, SD rats modeled with monocrotaline were treated with CeO2@BSA, and the therapeutic efficacy was evaluated using echocardiography, right cardiac catheterization, and HE staining sections.

Results: The outstanding ROS scavenging ability and biocompatibility of the ultrasmall CeO2@BSA nanocluster were confirmed in PMECs under hypoxia. CeO2@BSA inhibited the proliferation and migration of PMECs and promoted apoptosis in hypoxia. The results of echocardiography, right cardiac catheter and HE staining showed that CeO2@BSA had significant therapeutic effect on PAH rats

Conclusion: The CeO2@BSA nanocluster could mitigate hypoxia-induced PMECs dysfunction, thus demonstrating great potential for the treatment of PAH.