Dual-function TA@CaCO3 nanomedicine targeting M2 macrophage lipid peroxidation sensitivity in rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is a globally prevalent autoimmune musculoskeletal disease that requires early-stage treatment. Initially, patients with RA exhibit elevated reactive oxygen species (ROS) levels and acidic conditions within the articular spaces. These two factors synergistically promote lipid peroxidation in M2 macrophages and lead to increased inflammation. Our work was then designed to engineer a multifunctional nanomedicine that targets the increased lipid peroxidation sensitivity of M2 macrophages. We successfully synthesized a calcium carbonate (CaCO₃)-based nanomedicine via a biomineralization approach involving tannic acid (TA) and poly(ethylene glycol)-b-poly(glutamic acid). The TA@CaCO₃ nanomedicine exhibited superior ability to neutralize acidity and scavenge ROS both in vitro and in vivo, effectively enhancing the lipid peroxidation resistance of M2 macrophages. Therefore, this nanomedicine significantly protected M2 macrophages and ameliorated the symptoms of arthritis, achieving therapeutic efficacy comparable to that of conventional methotrexate therapy. This study proposes a therapeutic strategy for regulating immunity by improving the pathological microenvironment within the joint cavity in rheumatoid arthritis patients.