Polymer-Encapsulated Catalase for Targeted Redox Regulation in Acute Liver Injury

Abstract

The liver plays a critical role in maintaining homeostasis, and its dysfunction can lead to severe conditions like acute liver injury (ALI), which is primarily caused by viral infections, toxins, and oxidative stress. Reactive oxygen species (ROS), especially hydrogen peroxide (H₂O₂), significantly drive hepatocyte injury, initiating oxidative stress and inflammation. Current antioxidants, such as N-acetylcysteine (NAC) and superoxide dismutase (SOD), show limited clinical efficacy due to poor targeting, instability, and toxicity. Catalase (CAT), an essential enzyme for H₂O₂ decomposition, represents a promising therapeutic for ALI; however, its clinical application faces challenges in stability, rapid degradation, and insufficient targeting. Here, a novel nanocapsule-based CAT delivery system (n(CAT)) is presented, formed through in situ radical polymerization using 2-methacryloyloxyethyl phosphorylcholine (MPC) and N-(3-aminopropyl)-methacrylamide hydrochloride (APM). This strategy significantly enhances CAT's stability, retains enzyme activity, and improves selective liver accumulation, particularly at inflammation sites. The results demonstrate that n(CAT) effectively reduces oxidative stress, minimizes inflammation, and facilitates liver repair in ALI and ischemia-reperfusion injury (IRI) models. These findings highlight the potential of n(CAT) as a promising platform for advanced antioxidant therapies targeting liver diseases, including hepatitis.