Multidimensional Regulatory Mechanism Of A Thermoresponsive Antioxidant Metal-Free Carbon Nanodot Hydrogel And Its Application In Restoring Ocular Surface Homeostasis

The pathological mechanisms of ocular surface diseases, such as dry eye disease (DED), are complex. Oxidative stress-induced inflammatory damage and cellular apoptosis are core factors leading to prolonged disease duration. Existing clinical interventions mostly focus on physical lubrication, lacking the ability to deeply repair the pathological microenvironment. This study aims to develop a metal-free carbon nanodot (F-CD) thermoresponsive hydrogel platform with multi-enzyme activity and physical characteristics adapted to the ocular surface. By efficiently scavenging reactive oxygen species (ROS) and extending drug action, we explore its potential in restoring ocular surface homeostasis and promoting tissue regeneration.

Eye & ENT Hospital, Fudan University

Monodisperse metal-free carbon nanodots (F-CDs) were synthesized via hydrothermal method and integrated into a thermoresponsive matrix for enhanced ocular surface adaptation. Molecularly, F-CDs’ scavenging efficacy against radicals (OH·, O^2-, DPPH) and their protection of mitochondrial function in human corneal epithelial cells were evaluated. In a BAC-induced dry eye mouse model, therapeutic efficacy was systematically verified through tear dynamics, corneal topography, histological examination of goblet cells and epithelial integrity, and inflammatory factor analysis.

The F-CD hydrogel demonstrated excellent biocompatibility and multi-target antioxidant capacity, with a free radical neutralization rate reaching approximately 80%. In the DED mouse model, the therapy exhibited significant synergistic effects: tear secretion in the treatment group significantly rose from an extremely low pathological level to near-physiological levels. The corneal epithelial repair process was markedly accelerated, with epithelial thickness increasing substantially, effectively reversing chemical stress-induced pathological damage. Molecular mechanism studies confirmed that the therapy down-regulated the expression of pro-inflammatory factors by more than 60%, blocking the "oxidative stress-inflammation" vicious cycle.

This study successfully developed an ophthalmic-specific nanodrug delivery system with both biological activity and physical adaptability. Through its unique "in situ gel retention" and "multi-target antioxidant" synergistic mechanisms, the F-CD hydrogel breaks through the dilemma where traditional drugs cannot penetrate deeply into pathological tissues and struggle to eradicate microenvironmental damage caused by oxidative stress at the source. This achievement not only expands the application scenarios of carbon dot materials in nanobiology but also provides a key technical path for the development of high-performance, high-safety, and clinically valuable ocular surface regenerative and reparative drugs.