The Role of ROS in Atherosclerosis and ROS-Based Nanotherapeutics for Atherosclerosis: Atherosclerotic Lesion Targeting, ROS Scavenging, and ROS-Responsive Activity

Atherosclerosis is a progressive inflammatory disease that is intimately associated with oxidative stress. Reactive oxygen species (ROS) are involved in various critical stages of atherogenesis including endothelial dysfunction, immune cell activation, and foam cell formation. In recent years, nanotherapeutic approaches have emerged as promising tools to regulate ROS levels due to their tunable physicochemical properties, stimuli-responsiveness, and lesion-targeting potential. This review presents an integrated summary of ROS generation and elimination mechanisms in atherosclerotic plaques and outlines recent developments in both ROS-scavenging and ROS-responsive nanoplatforms. Instead of viewing these approaches in isolation, we emphasize their combinatorial potential to enhance therapeutic precision. Key challenges, including biosafety, pharmacokinetics, and off-target effects, are critically discussed. Lastly, we provide perspectives on the future design of intelligent, multifunctional, and clinically translatable ROS-modulating nanotherapeutics for effective atherosclerosis treatment.