Nanoceria-Mediated Cyclosporin A Delivery for Dry Eye Disease Management through Modulating Immune–Epithelial Crosstalk
Wenyu Cui, Sheng Chen, Tianyi Hu, Tinglian Zhou, Chen Qiu, Luyang Jiang, Xiaoyu Cheng, Jian Ji, Ke Yao, Haijie Han
Abstract
Dry eye disease (DED) affects a substantial worldwide population with increasing frequency. Current single-targeting DED management is severely hindered by the existence of an oxidative stress–inflammation vicious cycle and complicated intercellular crosstalk within the ocular microenvironment. Here, a nanozyme-based eye drop, namely nanoceria loading cyclosporin A (Cs@P/CeO 2 ), is developed, which possesses long-term antioxidative and anti-inflammatory capacities due to its regenerative antioxidative activity and sustained release of cyclosporin A (CsA). In vitro studies showed that the dual-functional Cs@P/CeO 2 not only inhibits cellular reactive oxygen species production, sequentially maintaining mitochondrial integrity, but also downregulates inflammatory processes and repolarizes macrophages. Moreover, using flow cytometric and single-cell sequencing data, the in vivo therapeutic effect of Cs@P/CeO 2 was systemically demonstrated, which rebalances the immune–epithelial communication in the corneal microenvironment with less inflammatory macrophage polarization, restrained oxidative stress, and enhanced epithelium regeneration. Collectively, our data proved that the antioxidative and anti-inflammatory Cs@P/CeO 2 may provide therapeutic insights into DED management.