Methotrexate-loaded multifunctional nanoparticles with near-infrared irradiation for the treatment of rheumatoid arthritis

Backgrounds: Despite the advances of rheumatoid arthritis (RA) therapeutics, several patients do not receive adequate treatment due to the toxicity and/or insufficient response of drugs. The aim of this study is to design photothermally controlled drug release from multifunctional nanoparticles (MNPs) at a near-infrared (NIR) irradiated site to improve therapeutic efficacy for RA and reduce side effects. Methods: Au film was deposited onto methotrexate (MTX)-loaded poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles, resulting in MTX-loaded MNPs. The synergistic effects of MTX-loaded MNPs with NIR irradiation were investigated using RA fibroblast-like synoviocytes (FLSs) and collagen-induced arthritis (CIA) mice. Results: Upon NIR irradiation, NIR resonance of the Au half-shell generated heat locally, accelerating MTX release from PLGA nanoparticles. In vivo NIR images of MTX-loaded MNPs indicated effective delivery of the MNPs to the inflamed joints. Moreover, in collagen-induced arthritis mice, MTX-loaded MNPs containing 1/1400 of MTX solution (repeated-dose administration) had therapeutic effects comparable to conventional treatment with MTX solution. In vitro experiments showed higher therapeutic efficacy of MTX-loaded MNPs with NIR irradiation than that of chemotherapy alone. Conclusions: A combination therapy of MTX-loaded MNP and NIR irradiation showed durable and good treatment efficacy for the suppression of arthritis in a single administration of small dose of MTX. Our results demonstrate that the treatment modality using drug-loaded MNP with NIR irradiation may be a promising therapeutic strategy for the treatment of RA and allow in vivo NIR optical imaging.