Reprogramming Macrophage Phenotype Using a Reactive Oxygen Species-Responsive Liposome Delivery System for...

Area of Science:

• Biomedical Engineering
• Immunology
• Pharmacology

Background:

• Osteoarthritis (OA) progression is driven by synovial inflammation.
• Macrophage polarization imbalance (M1/M2) significantly contributes to OA pathogenesis.

Purpose of the Study:

• To develop a reactive oxygen species (ROS)-responsive liposome system for targeted delivery of dimethyl fumarate (DMF).
• To reprogram M1-polarized macrophages and mitigate the inflammatory microenvironment in OA.
• To evaluate the therapeutic efficacy of DMF-loaded liposomes in an OA mouse model.

Main Methods:

• Fabrication of ROS-responsive liposomes functionalized with folic acid for M1 macrophage targeting.
• In vitro assessment of liposome biocompatibility, stability, ROS scavenging, and macrophage polarization modulation via the Nrf2/HO-1 pathway.
• In vivo evaluation of liposome efficacy in an anterior cruciate ligament transection (ACLT)-induced OA mouse model, assessing synovial inflammation, cartilage damage, and subchondral bone changes.

Main Results:

• Liposomes demonstrated favorable physicochemical properties, stability, and biocompatibility.
• DMF-loaded liposomes effectively reduced ROS levels in M1 macrophages, promoting polarization shift and reducing chondrocyte inflammation and apoptosis.
• In vivo studies showed significant reduction in synovial inflammation, cartilage protection, reversal of subchondral bone alterations, and slowed OA progression in ACLT mice.

Conclusions:

• ROS-responsive liposomes targeting M1 macrophages offer a promising strategy for OA treatment.
• This targeted drug delivery system effectively modulates the inflammatory milieu, ameliorating OA pathology.
• The developed liposomal DMF formulation presents a potential therapeutic avenue for osteoarthritis management.