Design of Diselenide-Bridged Hyaluronic Acid Nano-antioxidant for Efficient ROS Scavenging to Relieve Colitis

Jiaqi Xu, Tianjiao Chu, Tingting Yu, Naishi Li, Chunling Wang, Chen Li, Yinlong Zhang, Huan Meng, Guangjun Nie

Research output: Contribution to journalArticlepeer-review

Abstract

Overproduction of reactive oxygen species (ROS), a key characteristic of inflammatory bowel disease (IBD), is responsible for dysregulation of signal transduction, inflammatory response, and DNA damage, which ultimately leads to disease progression and deterioration. Thus, ROS scavenging has become a promising strategy to navigate IBD. Inspired by the targeting capability of hyaluronic acid (HA) to CD44-overexpressed inflammatory cells together with the redox regulation capacity of diselenide compounds, we developed an oral nanoformulation, i.e., diselenide-bridged hyaluronic acid nanogel (SeNG), with a view to treat colitis through a ROS scavenging mechanism. Our data demonstrated that SeNG specifically accumulated in colitis tissue that was mediated by highly efficient CD44-HA interaction. This has allowed us to demonstrate a significant anti-inflammatory effect in an acute colitis mouse model induced by dextran sulfate sodium and trinitrobenzenesulfonic acid. Mechanistically, we continued to show SeNG reduced the ROS level via both direct elimination and up-regulation of the Nrf2/HO-1 signal pathway. Collectively, our work provides proof-of-principle evidence for a SeNG-mediated nano-antioxidant strategy, by which colitis could be effectively managed.

Original languageEnglish (US)
Pages (from-to)13037-13048
Number of pages12
JournalACS Nano
Volume16
Issue number8
DOIs
StatePublished - Aug 23 2022

Keywords

  • colitis
  • diselenide-bridged nanogel
  • nano-antioxidant
  • Nrf-2/HO-1
  • ROS scavenger

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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