Remodeling immune microenvironment in periodontitis using resveratrol liposomes as an antibiotic-free therapeutic strategy

J Nanobiotechnology. 2021 Dec 20;19(1):429. doi: 10.1186/s12951-021-01175-x.

Abstract

Background: Periodontitis is a complicated inflammatory disease that damages the tooth-supporting tissues, with limited pharmacotherapy available. Macrophage-targeting therapy is promising for inflammatory diseases. Resveratrol (RSV), a nonflavonoid polyphenol, is known for its anti-inflammatory and immunomodulatory effects. However, its medical application is limited by its poor stability and water-solubility, as well as its low bioavailability.

Result: A therapeutic resveratrol-loaded liposomal system (Lipo-RSV) was developed to treat periodontitis. The physical properties of Lipo-RSV and its ability to regulate macrophages were investigated. The results showed that Lipo-RSV had good biocompatibility and could re-educate the inflammatory macrophages from M1- to M2-like phenotype through activating p-STAT3 and downregulating p-STAT1. Besides, the Lipo-RSV could scavenge ROS and inhibit the NF-κB signal and inflammasomes, thereby reducing the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α.

Conclusion: These results revealed that Lipo-RSV could be a potential therapeutic system for the antibiotic-free treatment for periodontal diseases.

Keywords: Immune microenvironment; Liposome; Local delivery; Macrophage; Periodontitis; Resveratrol.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Biocompatible Materials / therapeutic use
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Down-Regulation / drug effects
  • Humans
  • Inflammasomes / drug effects
  • Inflammasomes / metabolism
  • Liposomes / chemistry*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • Periodontitis / drug therapy*
  • Periodontitis / immunology
  • Resveratrol / chemistry
  • Resveratrol / pharmacology
  • Resveratrol / therapeutic use*
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Biocompatible Materials
  • Cytokines
  • Inflammasomes
  • Liposomes
  • NF-kappa B
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Resveratrol