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Systemic Inflammation Modulates Clearance and Drives Extra-Hepatic Distribution of Extracellular Vesicles.

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Systemic inflammation dramatically alters extracellular vesicle (EV) biodistribution, significantly extending their plasma half-life and enriching them in inflamed organs like the liver and spleen. However, functional therapeutic cargo delivery via EVs remained limited in this study.

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Area of Science:

  • Biomedical Engineering
  • Immunology
  • Nanomedicine

Background:

  • Extracellular vesicles (EVs) are key for targeted therapeutic delivery.
  • Inflammation is central to many diseases, necessitating understanding of EV behavior in these conditions.

Purpose of the Study:

  • To investigate how acute systemic inflammation affects EV biodistribution, clearance, and plasma half-life.
  • To explore the role of macrophages and EV protein corona in these inflammatory changes.

Main Methods:

  • Utilized a lipopolysaccharide (LPS)-induced inflammation model in wild-type mice.
  • Employed bioluminescent and fluorescent labeling of EVs to track biodistribution.
  • Analyzed EV protein corona composition.

Main Results:

  • Inflammation extended EV plasma half-life by over 600-fold (2h) and 900-fold (24h).
  • EVs showed significant enrichment in inflamed organs (liver, spleen) and increased targeting of immune and epithelial cells.
  • Inflammation remodeled the EV protein corona with enrichment of acute-phase proteins and complement factors.
  • Despite increased uptake, functional in vivo EV cargo delivery was limited.

Conclusions:

  • Acute systemic inflammation profoundly alters EV biodistribution and immune cell interactions.
  • EV protein corona remodeling is linked to altered biodistribution under inflammation.
  • Challenges remain in achieving effective in vivo EV cargo delivery in inflammatory settings.