Targeted chemo-photothermal treatments of rheumatoid arthritis using gold half-shell multifunctional nanoparticles.

We have developed RGD-attached gold (Au) half-shell nanoparticles containing methotrexate (MTX) for the treatment of rheumatoid arthritis (RA), where MTX is the most widely used disease-modifying anti-rheumatic drug (DMARD) for the treatment of RA, and RGD peptide is a targeting moiety for inflammation. Upon near-infrared (NIR) irradiation, heat is locally generated due to Au half-shells, and the drug release rate is enhanced, delivering heat and drug to the inflamed joints simultaneously. RA is a chronic inflammatory disease characterized by synovial inflammation in multiple joints within the penetration depth of NIR light. When combined with NIR irradiation, these nanoparticles containing a much smaller dosage of MTX (1/930 of MTX solution) showed greater therapeutic effects than that of a conventional treatment with MTX solution in collagen-induced arthritic mice. This novel drug delivery system is a good way to maximize therapeutic efficacy and minimize dosage-related MTX side effects in the treatment of RA. Furthermore, these multifunctional nanoparticles could be applied to other DMARDs for RA or other inflammatory diseases.