Targeted therapy of atherosclerosis by pH-sensitive hyaluronic acid nanoparticles co-delivering all-trans retinal and rapamycin.

Atherosclerosis, the leading cause of death in the elderly worldwide, is typically characterized by elevated reactive oxygen species (ROS) levels and a chronic inflammatory state at the arterial plaques. Herein, pH-sensitive nanoparticles (HR NPs) co-delivering all-trans retinal (ATR), an antioxidant linked to hyaluronic acid (HA) through a pH-sensitive hydrazone bond, and rapamycin (RAP), an anti-atherosclerotic drug loaded into the nanoparticle core, are developed for targeted combination therapy of atherosclerosis. In this way, HR NPs might simultaneously reduce ROS levels ATR antioxidant activity and reduce inflammation the anti-inflammatory effect of RAP.