Nanozyme-Based Therapeutic Strategies in Atherosclerosis: Mechanistic Insights, Targeting Approaches and Translational Challenges.

Atherosclerosis is a gradual process that occurs on the artery walls caused by multiple drivers, such as the presence of oxidative stress, chronic inflammation and disorganized lipid metabolism resulting in increased plaque formation and life-threatening cardiovascular disease. Due to their poor bioavailability, rapid clearance from the body and inability to maintain catalytic activity over time, traditional antioxidant drugs have reported minimal clinical success. Conversely, nanozyme-based therapeutics are being investigated as a new approach to treat atherosclerosis. Nanozymes are specially designed nanomaterials that have innate enzyme-like behaviors (e.g., superoxide dismutase-like, catalase-like, and peroxidase-like) which allow them to persistently scavenge for reactive oxygen species (ROS) through their multiple catalytic pathways. As a result of their innate catalytic activity, nanozymes can modulate numerous key pathophysiological processes associated with atherosclerosis, such as endothelial dysfunction, low-density lipoprotein oxidation, foam cell formation, and plaque progression. Furthermore, new nanozyme systems are being designed with targeting abilities to improve lesion-specific delivery and reduce the chance of off-target action. Numerous animal studies have demonstrated that these nanozymes significantly reduced oxidative stress and inflammatory signaling in addition to reducing the overall plaque load, indicating their potential as agents for therapeutic intervention. While there has been considerable advancement, there remain unresolved issues that still exist in the domains of biosafety, pharmacokinetics, large-scale manufacturing and clinical translation related to their use. Nanozyme based platforms are based on a multi-functional and mechanistic integration of various therapies that may redefine future therapies used to manage atherosclerosis.