Natural Targeting Potent ROS-eliminating Tungsten-based Polyoxometalate Nanodots for Efficient Treatment of Pulmonary Hypertension.

Pulmonary hypertension (PH) is a disease of pulmonary artery stenosis and blockage caused by abnormal pulmonary artery smooth muscle cells (PASMCs), with high morbidity and mortality. Current treatment methods only relieve symptoms by reducing pulmonary vascular pressure, but cannot fundamentally solve the problem of pulmonary artery stenosis. High levels of reactive oxygen species (ROS) in pulmonary arteries play a crucial role in inducing phenotypic transformation and abnormal proliferation of PASMCs. However, antioxidants are rarely approved for the treatment of PH because of lack of targeting and low bioavailability. In this study, we revealed the presence of an enhanced permeability and retention effect (EPR) -like effect in pulmonary arteries of PH by tissue transmission electron microscopy (TEM). Subsequently, for the first-time, we developed tungsten-based polyoxometalate nanodots (WNDs) with potent elimination of multiple ROS for efficient treatment of PH thanks to the high proportion of reduced W 5+ . WNDs were effectively enriched in the pulmonary artery by intravenous injection because of the EPR-like effect of PH, and significantly prevented the abnormal proliferation of PASMCs, greatly improved the remodeling of pulmonary arteries, and ultimately improved right heart function. In conclusion, this work provides a novel and effective solution to the dilemma of targeting ROS for treatment of PH. This article is protected by copyright. All rights reserved.