%0 Journal Article
%T Nanoceria-Mediated Cyclosporin A Delivery for Dry Eye Disease Management through Modulating Immune-Epithelial Crosstalk.
%A Cui W
%A Chen S
%A Hu T
%A Zhou T
%A Qiu C
%A Jiang L
%A Cheng X
%A Ji J
%A Yao K
%A Han H
%J ACS Nano
%V 18
%N 17
%D 2024 Apr 30
%M 38632691
%F 18.027
%R 10.1021/acsnano.3c11514
%X 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/CeO2), 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/CeO2 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/CeO2 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/CeO2 may provide therapeutic insights into DED management.