Combining MSC Exosomes and Cerium Oxide Nanocrystals for Enhanced Dry Eye Syndrome Therapy.

Abstract

Dry eye syndrome (DES) is a prevalent ocular disorder involving diminishe·d tear production and increased tear evaporation, leading to ocular discomfort and potential surface damage. Inflammation and reactive oxygen species (ROS) have been implicated in the pathophysiology of DES. Inflammation is one core cause of the DES vicious cycle. Moreover, there are ROS that regulate inflammation in the cycle from the upstream, which leads to treatment failure in current therapies that merely target inflammation. In this study, we developed a novel therapeutic nanoparticle approach by growing cerium oxide (Ce) nanocrystals in situ on mesenchymal stem cell-derived exosomes (MSCExos), creating MSCExo-Ce. The combined properties of MSCExos and cerium oxide nanocrystals aim to target the "inflammation-ROS-injury" pathological mechanism in DES. We hypothesized that this approach would provide a new treatment option for patients with DES. Our analysis confirmed the successful in situ crystallization of cerium onto MSCExos, and MSCExo-Ce displayed excellent biocompatibility. In vitro and in vivo experiments have demonstrated that MSCExo-Ce promotes corneal cell growth, scavenges ROS, and more effectively suppresses inflammation compared with MSCExos alone. MSCExo-Ce also demonstrated the ability to alleviate DES symptoms and reverse pathological alterations at both the cellular and tissue levels. In conclusion, our findings highlight the potential of MSCExo-Ce as a promising therapeutic candidate for the treatment of DES.