Albumin mediated reactive oxygen species scavenging and targeted delivery of methotrexate for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. Although there are a variety of treatments for RA, the substantial clinical therapies are still limited to disease-modifying anti-rheumatic drugs (DMARD), which would induce obvious side-effect in patients after long-term administration. Herein, an uncomplicated drug-induced self-assembly strategy was proposed to fabricate enzyme-loaded albumin nanomedicine. The hydrophobic drug methotrexate (MTX) could induce self-assembly of superoxide dismutase (SOD) and human serum albumin (HSA) to form HSA-SOD-MTX nanoparticle. After intravenous injection, dual-modal imaging including fluorescence imaging or single-photon emission computed tomography (SPECT)/CT imaging exhibits high accumulation of cyanine 5.5 (Cy5.5) or ¹²⁵I labeled HSA-SOD-MTX nanoparticles in the joints of collagen-induced arthritis (CIA) mice. Importantly, using the synergy therapy of SOD enzyme to scavenge the reactive oxygen species (ROS) and MTX to suppress inflammation, HSA-SOD-MTX nanoparticles exhibit excellent therapeutic efficiency of RA in CIA mice compared with the other groups. Micro-CT and clinical arthritis score of RA mice further demonstrate that RA symptoms of mice treated with HSA- SOD-MTX nanoparticles is significantly relived, which was further demonstrated by the histological analysis and the inflammatory factors measurement. The synergy therapy of inflammation by MTX and SOD enzyme based on HSA-SOD-MTX nanoparticles show excellent therapeutic effects of RA without inducing obvious side effects. Therefore, our strategy may further promote the highly efficient therapy of RA using SOD enzyme to scavenge the ROS and decreasing the side-effect of MTX, which may provide the reference for clinical RA treatment.