A glutathione-responsive silica-based nanosystem capped with in-situ polymerized cell-penetrating poly(disulfide)s for precisely modulating immuno-inflammatory responses

Xuan Li, Chuan Wang, Leilei Wang, Regina Huang, Wai Chung Li, Xinna Wang, Sarah Sze Wah Wong, Zongwei Cai, Ken Cham Fai Leung*, Lijian Jin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Hypothesis: Precise modulation of immuno-inflammatory response is crucial to control periodontal diseases and related systemic comorbidities. The present nanosystem with the controlled-release and cell-penetrating manner enhances the inflammation modulation effects of baicalein in human gingival epithelial cells (hGECs) for better oral healthcare. 

Experiments: We constructed a red-emissive mesoporous silica nanoparticle-based nanosystem with cell-penetrating poly(disulfide) (CPD) capping, through a facile in-situ polymerization approach. It was featured with a glutathione-responsive manner and instant cellular internalization capacity for precisely delivering baicalein intracellularly. Laboratory experiments assessed whether and how the nanosystem per se with the delivered baicalein could modulate immuno-inflammatory responses in hGECs. 

Findings: The in-situ polymerized CPD layer capped the nanoparticles and yet controlled the release of baicalein in a glutathione-responsive manner. The CPD coating could facilitate cellular internalization of the nanosystem via endocytosis and thiol-mediated approaches. Notably, the intracellularly released baicalein effectively downregulated the expression of pro-inflammatory cytokines through inhibiting the NF-κB signaling pathway. The nanosystem per se could modulate immuno-inflammatory responses by passivating the cellular response to interlukin-1β. This study highlights that the as-synthesized nanosystem may serve as a novel multi-functional vehicle to modulate innate host response via targeting the NF-κB pathway for precision healthcare.

Original languageEnglish
Pages (from-to)322-336
Number of pages15
JournalJournal of Colloid and Interface Science
Volume614
DOIs
Publication statusPublished - 15 May 2022

Scopus Subject Areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Surfaces, Coatings and Films
  • Colloid and Surface Chemistry

User-Defined Keywords

  • Cell-penetrating poly(disulfide)s
  • Immunomodulation
  • Intracellular drug delivery
  • Mesoporous silica nanoparticles
  • Periodontal disease

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