Globally, age-related cataracts are one of the main causes of visual impairment and blindness [1,2]. With the increasing aging of the global population, their prevalence continues to rise. In some developed countries, among individuals aged 65 and above, the prevalence of cataracts exceeds 50 % [3]. In developing countries, due to large population bases and accelerated aging, cataracts account for over 90 % of total disability-adjusted life years lost [3]. The main characteristic of this disease is a gradual decline in lens transparency, resulting in progressive vision loss. Currently, the most effective treatment is phacoemulsification with intraocular lens (IOL) implantation [4,5]. However, this procedure carries risks of intraoperative and postoperative complications, including posterior capsular rupture, corneal endothelial damage, iris damage, endophthalmitis, displacement or dislocation [6,7]. Meanwhile, alternative cataract treatments remain largely in the preclinical stage. Therefore, by exploring cataract pathogenesis, we can potentially achieve significant social benefits in terms of patient health and healthcare efficiency.

Oxidative stress plays a pivotal role in the pathogenesis of age-related cataracts [8,9]. The antioxidant defense system in the eye weakens with age, leading to an imbalance between reactive oxygen species (ROS) production and clearance [[10], [11], [12]]. These ROS attack critical biomolecules in the lens, including proteins, lipids, and nucleic acids, resulting in structural and functional alterations of lens proteins that ultimately lead to their aggregation and denaturation [13,14]. In addition to age itself, there are several risk factors associated with age-related cataract. Prolonged exposure to ultraviolet (UV) radiation, smoking and nutritional deficiencies all increase the risk of age-related cataracts [15]. Ultraviolet radiation can directly damage the lens, and smoking can affect ocular blood circulation and increase oxidative stress [16]. And nutritional deficiencies, especially the lack of antioxidants such as vitamin C, vitamin E and carotenoids [17,18], will weaken the antioxidant defense ability of the lens.

Epigallocatechin gallate (EGCG), an FDA-approved polyphenolic catechin, is the most abundant and bioactive compound in tea polyphenols [19]. Its structure combines a catechin backbone with a gallic acid moiety, conferring potent antioxidant properties [[20], [21], [22]]. EGCG has strong antioxidant capacity. It can scavenge free radicals (e.g., superoxide and hydroxyl radicals) by hydrogen donation, protecting biomolecules (DNA, proteins, lipids) from oxidative damage [[23], [24], [25]]. Additional studies have demonstrated the impact of polyphenols on the conformational changes of proteins and EGCG's efficacy in inhibiting human crystallin aggregation under acidic pH and elevated temperatures, effectively reducing the formation of β-sheet-rich fibrillar aggregates [[26], [27], [28]]. Despite promising therapeutic potential in various diseases, EGCG faces clinical challenges, including low bioavailability and stability limitations [29].

Polyphenol substances similar to EGCG form supramolecular networks through coordination with metal ions. Metal-phenolic networks (MPNs) have attracted extensive interest due to their one-step formation, high biocompatibility and versatility [30,31]. MPNs demonstrate simple aqueous-based synthesis through various self-assembly methods (direct, template-directed, emulsion-mediated, and nanocoating) without requiring special conditions or organic solvents. These networks exhibit excellent drug-loading capacity, biocompatibility, and unique properties including pH/redox responsiveness and substrate-independent adhesion. In biomedical applications, MPNs serve as versatile platforms for multimodal tumor imaging and combination cancer therapies (photothermal, photodynamic, chemodynamic and radiotherapy). Their ability to integrate multiple treatment modalities enhances therapeutic efficacy, making them promising multifunctional materials for targeted drug delivery [32,33].

As a metal ion, Zn2+ also has many applications in antioxidation. First of all, Zn2+ serves as an essential cofactor of copper/zinc-superoxide dismutase (Cu/Zn-SOD), which clears free radicals by converting superoxide anion free radicals into hydrogen peroxide and oxygen, thereby protecting biological macromolecules such as DNA, proteins, and lipids [34]. Secondly, Zn2+ can stabilize biological membrane structures such as cell membranes and mitochondrial membranes, resist the invasion of external oxidizing substances, reduce intracellular ROS generation and antioxidant leakage [35]. Therefore, adding Zn2+ to drugs can enhance the antioxidant effect and help maintain human health. Upon forming EGCG-Zn complexes, Zn2+ coordinates with phenolic hydroxyl groups or other functional groups in EGCG molecules [36]. This interaction stabilizes the molecular structure of EGCG to a certain extent, reduces its degradation in physiological environments, and enables it to exert antioxidant function more durably. In terms of synergistic antioxidation, EGCG can provide hydrogen atoms through phenolic hydroxyl groups to scavenge free radicals, while Zn2+ can regulate the redox state inside cells and enhance the cell's resistance to oxidative stress [37,38]. This synergistic effect makes the overall antioxidant capacity of the EGCG-Zn complex higher than that of EGCG alone.

Based on the above research status, this study selects EGCG as the therapeutic drug and Zn2+ as the metal core to construct EGCG-Zn nanoparticles with a structure analogous to MPNs. These nanoparticles were designed to synergistically scavenge ROS (Schematic 1). The product is characterized by methods such as dynamic light scattering (DLS), UV–Vis spectroscopy, and transmission electron microscopy (TEM) to evaluate the particle size, potential, and chemical structure of EGCG-Zn. Subsequently, the in vitro safety and cell uptake ability of EGCG-Zn were verified in human corneal epithelial cells (HCECs) and lens epithelial cells (SRA 01/04). H2O2 is used to simulate ROS to establish an oxidative stress model, and the resistance of EGCG-Zn to cell damage and its antioxidant mechanism in organelles and cytoskeletons are verified in cells under oxidative stress. Finally, after confirming the feasibility of formulating EGCG-Zn nanoparticles into topical eye drops, their therapeutic potential was tested in a UV-B-induced cataract model, where lens opacity was quantified to evaluate their efficacy in inhibiting cataract progression.