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The progression of osteoarthritis (OA) is closely linked to synovial inflammation caused by an imbalance between M1 and M2 macrophages. To tackle this problem, we developed a liposome responsive to reactive oxygen species (ROS), modified with folic acid ligands to target M1-polarized macrophages, and loaded with the anti-inflammatory agent dimethyl fumarate (DMF). This liposome-based drug delivery system was designed to reprogram macrophage phenotype to remodel the inflammatory microenvironment in the joint cavity and alleviate OA degeneration. The liposome we prepared had a suitable size and negative zeta potential, with uniform size, good stability in aqueous solution, and excellent biocompatibility. Laboratory tests showed that these DMF-filled liposomes notably decreased high levels of ROS in M1-type macrophages and shifted macrophage polarization via the Nrf2/HO-1 pathway, which in turn lessened inflammation in chondrocytes and averted their apoptosis. Additionally, animal studies demonstrated that liposomes containing DMF exhibited notable anti-inflammatory properties, significantly reduced synovial inflammation, safeguarded injured cartilage, reversed changes in subchondral bone, and effectively slowed the progression of osteoarthritis in a mouse model induced by anterior cruciate ligament transection (ACLT). Therefore, ROS-responsive liposomes targeting M1-polarized macrophages represent a promising and valuable approach for OA treatment.
Lai et al. (Mon,) studied this question.