Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease accompanied by energy depletion and accumulation of reactive oxygen species (ROS). Inorganic nanoparticles (NPs) offer great promise for the treatment of RA because they mostly have functions beyond being drug carriers. However, conventional nanomaterials become coated with a protein corona (PC) or lose their cargo prematurely in vivo, reducing their therapeutic efficacy. To avoid these problems, we loaded methotrexate (MTX) into hollow structured manganese dioxide nanoparticles (H-MnO2 NPs), then coated them with a 'pseudo-corona' of human serum albumin (HSA) at physiological concentrations to obtain HSA-MnO2@MTX NPs. Efficacy of MTX, MnO2@MTX, and HSA-MnO2@MTX NPs was compared in vitro and in vivo. Compared to MnO2@MTX, HSA-coated NPs were taken up better by lipopolysaccharide-activated RAW264.7 and were more effective at lowering levels of pro-inflammatory cytokines and preventing ROS accumulation. HSA-MnO2@MTX NPs were also more efficient at blocking the proliferation and migration of fibroblast-like synoviocytes from rats with collagen-induced arthritis. In this rat model, HSA-MnO2@MTX NPs showed better biodistribution than other treatments, specifically targeting the ankle joint. Furthermore, HSA-MnO2@MTX NPs reduced swelling in the paw, regulated pro-inflammatory cytokine production, and limited cartilage degradation and signs of inflammation. These results establish the therapeutic potential of HSA-MnO2@MTX NPs against RA.