Wang Jiahao, Zhang Renjie, Xie Hongying, Yang Yuexin, Chen Hao, Lin Quankui
National Engineering Research Center of Ophthalmology and Optometry, School of Biomedical Engineering, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
National Engineering Research Center of Ophthalmology and Optometry, School of Biomedical Engineering, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
J Control Release. 2025 Jul 10;383:113798. doi: 10.1016/j.jconrel.2025.113798. Epub 2025 May 2.
In cataract, oxidative stress plays an important role. It breaks the balance of the antioxidant defense system by destroying biological macromolecules such as proteins, lipids and nucleic acids in the lens, induces lens opacity, and then leads to the formation of cataract. The antioxidant properties of epigallocatechin gallate (EGCG) are well-established, particularly its ability to scavenge ROS and modulate cellular pathways. However, its therapeutic potential is limited by poor stability and bioavailability. To overcome these challenges, the work is designed to form a metal-phenolic network (MPN) system by coordinating EGCG with zinc ions. MPNs offer distinct advantages for ocular drug delivery, including enhanced structural stability, improved cellular uptake, and the ability to simultaneously target multiple oxidative stress pathways. By doing so, an antioxidant nanoparticle is formed to slow down the turbidity process of the lens induced by oxidative stress and thus prevent the occurrence of cataract. The particle size, zeta potential, ultraviolet absorption spectrum, FTIR, surface morphology and element distribution of EGCG-Zn were determined. In vitro, EGCG-Zn has good biosafety, cell uptake performance and anti-cell damage performance. In addition, from a mechanistic analysis, the particles can scavenge free radicals and reduce the production of intracellular ROS. Similarly, EGCG-Zn can well prevent the damage of reactive oxygen species to intracellular lysosomes, mitochondria, cytoskeleton, DNA synthesis and cell senescence. In the UV-B-induced cataract animal model in rats, EGCG-Zn has good in vivo safety. The transparency of the lens in the experimental group using EGCG-Zn is significantly lower than that in the untreated model group. In conclusion, EGCG-Zn nanoparticles are expected to become an important means in the field of cataract treatment, bringing hope for restoring clear vision to many cataract patients.
在白内障形成过程中，氧化应激起着重要作用。它通过破坏晶状体中的蛋白质、脂质和核酸等生物大分子，打破抗氧化防御系统的平衡，诱导晶状体混浊，进而导致白内障的形成。表没食子儿茶素没食子酸酯（EGCG）的抗氧化特性已得到充分证实，尤其是其清除活性氧（ROS）和调节细胞信号通路的能力。然而，其治疗潜力受到稳定性差和生物利用度低的限制。为了克服这些挑战，本研究旨在通过EGCG与锌离子配位形成金属-酚网络（MPN）系统。MPN在眼部药物递送方面具有独特优势，包括增强的结构稳定性、改善的细胞摄取以及同时靶向多种氧化应激途径的能力。通过这样做，形成了一种抗氧化纳米颗粒，以减缓氧化应激诱导的晶状体混浊过程，从而预防白内障的发生。测定了EGCG-Zn的粒径、zeta电位、紫外吸收光谱、傅里叶变换红外光谱（FTIR）、表面形态和元素分布。在体外，EGCG-Zn具有良好的生物安全性、细胞摄取性能和抗细胞损伤性能。此外，从机理分析来看，该颗粒可以清除自由基并减少细胞内ROS的产生。同样，EGCG-Zn可以很好地防止活性氧对细胞内溶酶体、线粒体、细胞骨架、DNA合成和细胞衰老的损伤。在紫外线B诱导的大鼠白内障动物模型中，EGCG-Zn具有良好的体内安全性。使用EGCG-Zn的实验组晶状体透明度明显低于未治疗的模型组。总之，EGCG-Zn纳米颗粒有望成为白内障治疗领域的重要手段，为众多白内障患者恢复清晰视力带来希望。
