Li Feifei, Gao Sai, Ma Rui, Zhang Yijia, Li Yuxi, Wu Dingqi, Han Zeren, Li Qian, He Qian, Li Jiarui, Dai Qiong, Xu An-Ding, Zhang Liyun, Liu Chaoyong, Lu Yunfeng
State Key Laboratory of Organic-Inorganic Composites, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, P. R. China.
Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, P. R. China.
Small. 2025 Jun;21(23):e2412349. doi: 10.1002/smll.202412349. Epub 2025 Apr 25.
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.
肝脏在维持体内平衡方面发挥着关键作用,其功能障碍可导致严重病症,如急性肝损伤(ALI),这主要由病毒感染、毒素和氧化应激引起。活性氧(ROS),尤其是过氧化氢(H₂O₂),显著驱动肝细胞损伤,引发氧化应激和炎症。目前的抗氧化剂,如N-乙酰半胱氨酸(NAC)和超氧化物歧化酶(SOD),由于靶向性差、稳定性低和毒性等问题,临床疗效有限。过氧化氢酶(CAT)是一种分解H₂O₂的关键酶,是ALI的一种有前景的治疗方法;然而,其临床应用在稳定性、快速降解和靶向性不足方面面临挑战。在此,提出了一种基于纳米胶囊的新型CAT递送系统(n(CAT)),它是通过使用2-甲基丙烯酰氧乙基磷酰胆碱(MPC)和N-(3-氨丙基)-甲基丙烯酰胺盐酸盐(APM)进行原位自由基聚合形成的。该策略显著提高了CAT的稳定性,保留了酶活性,并改善了肝脏的选择性积累,尤其是在炎症部位。结果表明,n(CAT)在ALI和缺血再灌注损伤(IRI)模型中有效降低氧化应激,减少炎症,并促进肝脏修复。这些发现突出了n(CAT)作为一种有前景的平台在针对包括肝炎在内的肝脏疾病的先进抗氧化治疗中的潜力。