ROS-triggered drug release of puerarin from boronic ester modified nanoparticles to reduce oxidative damage in HUVECs

Abstract

Endothelial dysfunction accompanied with oxidative stress and inflammation is an early event in the progression of atherosclerosis. Puerarin (PUE) is a water-insoluble isoflavone and Chinese herbal compound for treatment of cardiovascular diseases. In the study, dextran modified with boronic ester groups (PHB-DEX) nanoparticles (NPs) with reactive oxygen species (ROS)-responsive properties were prepared for PUE delivery that might improve the bioavailability of PUE and provide the selective treatment in different stages of atherosclerosis. The characteristic functional groups and thermal properties of PHB-DEX were analyzed. The hydrodynamic size of PHB-DEX NPs containing PUE (PUE-NPs) was ∼218.7 nm with negative charge (−12.2 mV) and sphere-like structure. The encapsulation efficiency of PUE in PHB- DEX NPs was ∼20.8%. The hydrolysis of developed NPs could be triggered by H2O2-induced oxidative stress. The cell viability of human umbilical vein endothelial cells (HUVECs) incubated with PUE-NPs (<50 μM) was significantly increased. Post-treatment of PUE-NPs (12.5, 25 and 50 μM) on H2O2-damaged HUVECs could reduce the inflammation (TNF, IL-1α, IL-6, MMP-3 and MMP-9) and apoptosis level. The cell viability was increased to normal level when incubation the damaged HUVECs with 50 μM of PUE-NPs. These results suggest that ROS-responsive PUE-NPs may have be a promising therapeutic approach for atherosclerosis.