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

You Jung Ha, Sun Mi Lee, Chin Hee Mun, Hyung Joon Kim, Yonghee Bae, Ji Hee Lim, Kyu Hyung Park, Soo Kon Lee, Kyung Hwa Yoo, Yong Beom Park

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21 Citations (Scopus)


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.

Original languageEnglish
Article number146
JournalArthritis Research and Therapy
Issue number1
Publication statusPublished - 2020 Jun 18

Bibliographical note

Funding Information:
This research was supported by a grant from MWH through the Korean Health Technology R&D Project (Grant No. A110905) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (Grant No. HI14C1324) and from MEST through the National Research Foundation (NRF) of Korea (Grant Nos. NRF-2016R1A2B3011980, NRF-2016R1A2B4014999, and NRF-2012R1A4A1029061).

Publisher Copyright:
© 2020 The Author(s).

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology


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