Nanoceria-Mediated Cyclosporin A Delivery for Dry Eye Disease Management through Modulating Immune-Epithelial Crosstalk.

ACS Nano

Eye Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou 310009, P. R. China.

Published: April 2024

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), is developed, which possesses long-term antioxidative and anti-inflammatory capacities due to its regenerative antioxidative activity and sustained release of cyclosporin A (CsA). studies showed that the dual-functional Cs@P/CeO 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 therapeutic effect of Cs@P/CeO 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 may provide therapeutic insights into DED management.

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Source
http://dx.doi.org/10.1021/acsnano.3c11514DOI Listing

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