Reprogramming peritoneal macrophages with outer membrane vesicle-coated PLGA nanoparticles for endometriosis...

Area of Science:

• Biomedical Engineering
• Immunology
• Women's Health

Background:

• Endometriosis is a chronic inflammatory condition affecting women of reproductive age.
• Current hormonal therapies are not suitable for conception, necessitating alternative treatments.
• Macrophages play a key role in endometriosis pathogenesis.

Purpose of the Study:

• To engineer outer membrane vesicle (OMV)-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (OMV-NPs) for endometriosis therapy.
• To evaluate the efficacy of OMV-NPs in modulating macrophage phenotype and inhibiting endometriosis progression in vivo.
• To investigate the correlation between M2 macrophages and fibrosis in endometriosis patients.

Main Methods:

• Engineered OMV-NPs by coating PLGA nanoparticles with bacterial outer membrane vesicles.
• Administered OMV-NPs in a mouse model of endometriosis.
• Analyzed macrophage uptake, phenotype (M1/M2 ratio), TGF-β1 production, and myofibroblast activation.
• Performed immunohistochemical analysis on patient tissues.

Main Results:

• OMV-NPs showed efficient internalization by peritoneal macrophages in vivo.
• Treatment with OMV-NPs significantly decreased the M2 to M1 macrophage ratio in the peritoneal cavity and endometriotic lesions.
• OMV-NP treatment reduced TGF-β1 production, suppressed myofibroblast activation, and inhibited endometriosis progression.
• A positive correlation was observed between M2-polarized macrophages and fibrosis in patient tissues.

Conclusions:

• OMV-NPs are a promising non-hormonal therapeutic strategy for endometriosis.
• Reprogramming macrophages from M2 to M1 phenotype is a viable approach to combat endometriosis.
• OMV-NPs demonstrate potential for clinical translation in managing endometriosis.