2. Academic Validation
  3. Reactive oxygen species-responsive dexamethasone-loaded nanoparticles for targeted treatment of rheumatoid arthritis via suppressing the iRhom2/TNF-α/BAFF signaling pathway

Reactive oxygen species-responsive dexamethasone-loaded nanoparticles for targeted treatment of rheumatoid arthritis via suppressing the iRhom2/TNF-α/BAFF signaling pathway

  • Biomaterials. 2020 Feb;232:119730. doi: 10.1016/j.biomaterials.2019.119730.
Rongrong Ni 1,  Guojing Song 2,  Xiaohong Fu 2,  Ruifeng Song 3,  Lanlan Li 3,  Wendan Pu 3,  Jining Gao 4,  Jun Hu 5,  Qin Liu 6,  Fengtian He 2,  Dinglin Zhang 7,  Gang Huang 8
Affiliations

Affiliations

  • 1 Department of Chemistry, College of Basic Medical Science, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
  • 2 Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
  • 3 Department of Chemistry, College of Basic Medical Science, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
  • 4 Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Chongqing Engineering Research Center for Biomaterials and Regenerative Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
  • 5 Department of Neurology, Southwest Hospital, Third Military Medical University (Amy Medical University), Chongqing, 400038, China.
  • 6 Biomedical Analysis Center, Third Military Medical University (Amy Medical University), Chongqing, 400038, China.
  • 7 Department of Chemistry, College of Basic Medical Science, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Department of Urology, Southwest Hospital, Third Military Medical University (Amy Medical University), Chongqing, 400038, China. Electronic address: [email protected].
  • 8 Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Third Military Medical University (Army Medical University), Chongqing, 400038, China. Electronic address: [email protected].
PMID: 31918224 DOI: 10.1016/j.biomaterials.2019.119730
Abstract

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that results in synovitis, cartilage destruction, and even loss of joint function. The frequent and long-term administration of anti-rheumatic drugs often leads to obvious adverse effects and patient non-compliance. Therefore, to specifically deliver dexamethasone (Dex) to inflamed joints and reduce the administration frequency of Dex, we developed Dex-loaded Reactive Oxygen Species (ROS)-responsive nanoparticles (Dex/Oxi-αCD NPs) and folic acid (FA) modified Dex/Oxi-αCD NPs (Dex/FA-Oxi-αCD NPs) and validated their anti-inflammatory effect in vitro and in vivo. In vitro study demonstrated that these NPs can be effectively internalized by activated macrophages and the released Dex from NPs significantly downregulated the expression of iRhom2, TNF-α, and BAFF in activated Raw264.7. In vivo experiments revealed that Dex/Oxi-αCD NPs, especially Dex/FA-Oxi-αCD NPs significantly accumulated at inflamed joints in collagen-induced arthritis (CIA) mice and alleviated the joint swelling and cartilage destruction. Importantly, the expression of iRhom2, TNF-α, and BAFF in the joint was inhibited by intravenous injection of Dex/Oxi-αCD NPs and Dex/FA-Oxi-αCD NPs. Collectively, our data revealed that Dex-loaded ROS-responsive NPs can target inflamed joints and attenuate arthritis, and the 'iRhom2-TNF-α-BAFF' pathway plays an important role in the treatment of RA with the NPs, suggesting that this pathway may be a novel target for RA therapy.

Keywords

BAFF; Nanotherapy; Reactive oxygen species; Rheumatoid arthritis; TNF-α; iRhom2.

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