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<p>Dry eye disease (DED) is the most prevalent ocular surface disorder, with dysregulation of reactive oxygen species (ROS) playing a pivotal role in its pathogenesis. Recent studies have highlighted that anti-oxidative biomaterial-based eye drops represent an effective therapeutic strategy for DED management. Herein, we developed anti-oxidative tannic acid (TA)-based zwitterionic nanogels (PTNG) via dynamic covalent chemistry for treating DED. A zwitterionic copolymer (PMPD) containing phenylboronic acid moieties was synthesized and utilized to form nanogels upon mixing with a TA solution at physiological pH through PBA-catechol complexation. The formation of PTNG effectively addressed the instability and high-dose toxicity issues associated with free TA. Moreover, PTNG exhibited remarkable ROS responsiveness and free radical scavenging activity, efficiently migrating intracellular oxidative stress and inhibiting NLRP3/Caspase-1/GSDMD pyroptosis signaling pathways. In a DED mouse model, topical administration of PTNG significantly alleviated corneal epithelial defects, squamous metaplasia, and inflammatory infiltration of the corneal stroma while promoting the restoration of conjunctival goblet cell numbers and MUC1 mucin secretion to normal levels. Therefore, the PBA-catechol dynamic covalent chemistry provides a robust strategy for developing polyphenol-based nanomedicine, and our zwitterionic PTNG can serve as a promising anti-oxidative eye drop for treating DED and other oxidative stress-related ocular diseases.</p> Graphical Abstract <p></p>

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Antioxidant Zwitterionic nanogels via dynamic covalent chemistry for alleviating dry eye syndrome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月28日

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  • Junrong Chen,
  • Yiyun Luo,
  • Liyuan Peng,
  • Tingting Wu,
  • Li Tang,
  • Kaihui Nan,
  • Ravin Narain,
  • Yangjun Chen

摘要

Dry eye disease (DED) is the most prevalent ocular surface disorder, with dysregulation of reactive oxygen species (ROS) playing a pivotal role in its pathogenesis. Recent studies have highlighted that anti-oxidative biomaterial-based eye drops represent an effective therapeutic strategy for DED management. Herein, we developed anti-oxidative tannic acid (TA)-based zwitterionic nanogels (PTNG) via dynamic covalent chemistry for treating DED. A zwitterionic copolymer (PMPD) containing phenylboronic acid moieties was synthesized and utilized to form nanogels upon mixing with a TA solution at physiological pH through PBA-catechol complexation. The formation of PTNG effectively addressed the instability and high-dose toxicity issues associated with free TA. Moreover, PTNG exhibited remarkable ROS responsiveness and free radical scavenging activity, efficiently migrating intracellular oxidative stress and inhibiting NLRP3/Caspase-1/GSDMD pyroptosis signaling pathways. In a DED mouse model, topical administration of PTNG significantly alleviated corneal epithelial defects, squamous metaplasia, and inflammatory infiltration of the corneal stroma while promoting the restoration of conjunctival goblet cell numbers and MUC1 mucin secretion to normal levels. Therefore, the PBA-catechol dynamic covalent chemistry provides a robust strategy for developing polyphenol-based nanomedicine, and our zwitterionic PTNG can serve as a promising anti-oxidative eye drop for treating DED and other oxidative stress-related ocular diseases.

Graphical Abstract