Dextran-shelled oxygen-loaded nanodroplets modulate macrophages killing and inflammatory response to Enterococcus...

Area of Science:

• Biomedical Engineering
• Wound Healing Research
• Nanomedicine

Background:

• Chronic wounds present challenges due to inflammation, infection, and hypoxia.
• Macrophages are critical for wound repair, managing bacterial load and signaling tissue regeneration.
• Dextran-shelled Oxygen-Loaded NanoDroplets (OLNDs) are emerging as potential therapeutics for hypoxic wound environments.

Purpose of the Study:

• To investigate the impact of OLNDs on bacterial killing by macrophages.
• To assess the modulation of inflammatory and angiogenic factors by OLNDs.
• To compare the effects of OLNDs and Oxygen-Free NanoDroplets (OFNDs) under normoxic and hypoxic conditions.

Main Methods:

• Murine (BMDM) and human (dTHP-1) macrophages were treated with OLNDs and OFNDs.
• Reactive oxygen species (ROS) and nitric oxide (NO) production were measured.
• Bacterial killing of Enterococcus faecalis (E. faecalis) was assessed.
• Secretion of inflammatory cytokines (TNFα, IL-6, IL-1β) and VEGF was quantified.

Main Results:

• Both OLNDs and OFNDs increased ROS production in BMDMs but not dTHP-1.
• OLNDs uniquely induced nitric oxide secretion in BMDMs.
• Both nanodroplets enhanced E. faecalis killing by BMDMs under both normoxia and hypoxia.
• Nanodroplets reduced E. faecalis-induced inflammatory cytokine secretion in dTHP-1.
• OLNDs, but not OFNDs, reduced hypoxia-induced VEGF increase.

Conclusions:

• OLNDs and OFNDs effectively promote bacterial killing by macrophages.
• The dextran shell of nanodroplets exhibits anti-inflammatory properties.
• OLNDs represent a promising adjuvant therapy for chronic wound healing by enhancing bacterial clearance and reducing inflammation.