A multifunctional Cerium-Rutin nanozyme for neuroprotection via coordinated modulation of oxidative stress and neuroinflammation in retinal detachment.

Authors

Feiyu Jin, Weicheng Shen, Mingxin Ren, Yaohan Guo, Yuanye Yan, Ziyang Ye, Yuewei Peng, Bochen Yao, Kai Dong

Published in

Journal of controlled release : official journal of the Controlled Release Society. Pages 115312. Aug 29, 2026. Epub Aug 29, 2026.

Abstract

Excessive oxidative stress and neuroinflammation caused by retinal detachment (RD) drive progressive photoreceptor degeneration, posing a major challenge to functional vision recovery even after successful anatomical reattachment. These limitations highlight the urgent need for alternative or adjunctive therapeutic strategies to protect photoreceptors. Here, smart supramolecular Cerium-Rutin nanoparticles (CRNPs) are developed for coordinated redox and immunomodulatory therapy in RD. CRNPs are constructed through the coordination assembly of cerium ions with the natural flavonoid Rutin, integrating the reversible Ce³⁺/Ce⁴⁺ redox-switching capacity with the intrinsic anti-inflammatory activity of Rutin. This supramolecular nanozyme platform enables dynamic regulation of oxidative and inflammatory homeostasis within the injured retina. In vitro, CRNPs protect microglial and photoreceptor cells by scavenging reactive oxygen species (ROS) and suppressing inflammatory activation, demonstrating both anti-inflammatory and cytoprotective effects. In vivo, CRNPs effectively preserve photoreceptor morphology, protect outer nuclear layer integrity, enhance retinal electrophysiological responses and vision function in an RD model. Mechanistically, CRNPs first mitigate oxidative stress, which in turn suppresses activation of the NLRP3/ASC/caspase-1 signaling pathway, thereby reducing pro-inflammatory microglial activation and limiting the release of inflammatory mediators. Collectively, this study establishes a redox-active nanozyme platform capable of restoring retinal homeostasis and mitigating neuroinflammation, providing a promising nanotherapeutic approach for the treatment of RD and other oxidative stress-associated neurodegenerative diseases.

PMID:
42668066
Bibliographic data and abstract were imported from PubMed on 30 Aug 2026.

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