Dandelion-derived vesicles-laden hydrogel dressings capable of neutralizing Staphylococcus aureus exotoxins for the care of invasive wounds

J Control Release. 2024 Apr:368:355-371. doi: 10.1016/j.jconrel.2024.02.045. Epub 2024 Mar 6.

Abstract

Delayed wound healing caused by bacterial infection remains a major challenge in clinical treatment. Exotoxins incorporated in bacterial extracellular vesicles play a key role as the disease-causing virulence factors. Safe and specific antivirulence agents are expected to be developed as an effective anti-bacterial infection strategy, instead of single antibiotic therapy. Plant-derived extracellular vesicle-like nanoparticles have emerged as promising therapeutic agents for skin diseases, but the elucidations of specific mechanisms of action and clinical transformation still need to be advanced. Here, dandelion-derived extracellular vesicle-like nanoparticles (TH-EVNs) are isolated and exert antivirulence activity through specifically binding to Staphylococcus aureus (S. aureus) exotoxins, thereby protecting the host cell from attack. The neutralization of TH-EVNs against exotoxins has considerable binding force and stability, showing complete detoxification effect in vivo. Then gelatin methacryloyl hydrogel is developed as TH-EVNs-loaded dressing for S. aureus exotoxin-invasive wounds. Hydrogel dressings demonstrate good physical and mechanical properties, thus achieving wound retention and controlled release of TH-EVNs, in addition to promoting cell proliferation and migration. In vivo results show accelerated re-epithelialization, promotion of collagen maturity and reduction of inflammation after treatment. Collectively, the developed TH-EVNs-laden hydrogel dressings provide a potential therapeutic approach for S. aureus exotoxin- associated trauma.

Keywords: Dandelion; Extracellular vesicle-like nanoparticles; GelMA hydrogel; Neutralization; S. aureus exotoxin; Wound dressing.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents*
  • Bandages
  • Exotoxins
  • Hydrogels / chemistry
  • Staphylococcal Infections* / drug therapy
  • Staphylococcus aureus
  • Taraxacum*
  • Wound Healing

Substances

  • Hydrogels
  • Exotoxins
  • Anti-Bacterial Agents
  • Anti-Infective Agents