2. Academic Validation
  3. Peptide-anchored neutrophil membrane-coated biomimetic nanodrug for targeted treatment of rheumatoid arthritis

Peptide-anchored neutrophil membrane-coated biomimetic nanodrug for targeted treatment of rheumatoid arthritis

  • J Nanobiotechnology. 2023 Jan 13;21(1):13. doi: 10.1186/s12951-023-01773-x.
Ni Yang # 1 2 3,  Miaomiao Li # 1 2 3,  Ling Wu # 4,  Yinhong Song # 2 3,  Shi Yu 3,  Yingying Wan 1 2 3,  Wenjing Cheng 1 2 3,  Baoye Yang 1 2 3,  Xiaoqin Mou 1 2 3,  Hong Yu 1 2 3,  Jing Zheng 4,  Xinzhi Li 5,  Xiang Yu 6 7 8
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China.
  • 2 Institute of Infection and Inflammation, China Three Gorges University, Yichang, 443002, China.
  • 3 College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China.
  • 4 The People's Hospital of China Three Gorges University, Yichang, 443099, China.
  • 5 College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China. lixinzhi@ctgu.edu.cn.
  • 6 Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China. yuxiangwl2008@sina.com.
  • 7 Institute of Infection and Inflammation, China Three Gorges University, Yichang, 443002, China. yuxiangwl2008@sina.com.
  • 8 College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China. yuxiangwl2008@sina.com.
  • # Contributed equally.
PMID: 36639772 DOI: 10.1186/s12951-023-01773-x
Abstract

Macrophage polarization determines the production of cytokines that fuel the initiation and evolution of rheumatoid arthritis (RA). Thus, modulation of macrophage polarization might represent a potential therapeutic strategy for RA. However, coordinated modulation of macrophages in the synovium and synovial fluid has not been achieved thus far. Herein, we develop a biomimetic ApoA-I mimetic peptide-modified neutrophil membrane-wrapped F127 polymer (R4F-NM@F127) for targeted drug delivery during RA treatment. Due to the high expression of adhesion molecules and chemokine receptors on neutrophils, the neutrophil membrane coating can endow the nanocarrier with synovitis-targeting ability, with subsequent recruitment to the synovial fluid under the chemotactic effects of IL-8. Moreover, R4F peptide modification further endows the nanocarrier with the ability to target the SR-B1 receptor, which is highly expressed on macrophages in the synovium and synovial fluid. Long-term in vivo imaging shows that R4F-NM@F127 preferentially accumulates in inflamed joints and is engulfed by macrophages. After loading of the anti-inflammatory drug celastrol (Cel), R4F-NM@F127-Cel shows a significant reduction in hepatotoxicity, and effectively inhibits synovial inflammation and alleviates joint damage by reprogramming macrophage polarization. Thus, our results highlight the potential of the coordinated targeted modulation of macrophages as a promising therapeutic option for the treatment of RA.

Keywords

Macrophage; Nanodrug; Neutrophil; Rheumatoid arthritis; Target therapy.

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