Self-Adaptive Hydrogen Nano-Delivery System in Glaucoma Management: Synergistic Antioxidation and Anti-inflammation Therapeutic Strategy

Glaucoma-induced optic nerve damage is known to be a leading cause of blindness worldwide, yet current therapies mainly focus on reducing intraocular pressure without paying significant attention to the oxidative stress and inflammation in ocular tissues. Here, we address this issue by developing a self-adaptive two-dimensional nanosheet that enables sustained hydrogen release in the ocular microenvironment. The nanoagent (termed HyNDs) is constructed by modifying the surface of hydrogenated silicene (SiH), a biocompatible nanosheet that self-decomposes to generate hydrogen under physiological conditions, with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymer. HyNDs exhibit excellent dispersity, making them suitable for ocular delivery, while the TPGS coating ensures prolonged hydrogen release through its shielding effect. We demonstrate that HyNDs can efficiently scavenge oxidative radicals and downregulate the expression of oxidative stress-associated biomarkers in both cellular and animal models, contributing to significantly reduced intraocular pressure. Additionally, the nanoagent exhibits negligible cytotoxicity and adverse effects on ocular tissues. This hydrogen-based therapeutic approach features a dual mechanism of intraocular pressure reduction and oxidative stress mitigation, thereby exhibiting attractive promise for advancing the clinical management of glaucoma.