Dual-ROS-scavenging and dual-lingering nanozyme-based eye drops alleviate dry eye disease.

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings. Highlights: Modification of dynamic covalent bonds based on borate bonds can improve the solubility and dispersion of Fe-based nanozymes in solution. The nanozyme-based eye drops enable reactive groups to bind to the chemical groups present in the mucin layer to confer carrier adhesion, thereby increasing the retention time of the carrier on the ocular surface. Nanozyme-based eye drops have synergistic effects on Fe-based nanozymes, and borate bonds effectively neutralize excess ROS in the microenvironment of the ocular surface, thereby reducing oxidative stress and direct oxidative damage. Nanozyme-based eye drops could effectively alleviate DED and may be a promising nanotherapeutic strategy for DED treatment. [ABSTRACT FROM AUTHOR]