Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis

Abstract

Rheumatoid arthritis is a common chronic inflammatory disorder and a major cause of disability. Despite the progress made with recent clinical use of anti-cytokine biologics, the response rate of rheumatoid arthritis treatment remains unsatisfactory, owing largely to the complexity of cytokine interactions and the multiplicity of cytokine targets. Here, we show a nanoparticle-based broad-spectrum anti-inflammatory strategy for rheumatoid arthritis management. By fusing neutrophil membrane onto polymeric cores, we prepare neutrophil membrane-coated nanoparticles that inherit the antigenic exterior and associated membrane functions of the source cells, which makes them ideal decoys of neutrophil-targeted biological molecules. It is shown that these nanoparticles can neutralize proinflammatory cytokines, suppress synovial inflammation, target deep into the cartilage matrix, and provide strong chondroprotection against joint damage. In a mouse model of collagen-induced arthritis and a human transgenic mouse model of arthritis, the neutrophil membrane-coated nanoparticles show significant therapeutic efficacy by ameliorating joint damage and suppressing overall arthritis severity.

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Fig. 1: Preparation and characterization of neutrophil-NPs.
Fig. 2: Neutrophil-NPs inhibit pro-arthritogenic factors in vitro.
Fig. 3: Neutrophil-NPs enhance cartilage penetration and confer chondroprotection.
Fig. 4: Neutrophil-NPs ameliorate joint destruction in a mouse model of collagen-induced arthritis and a human transgenic mouse model of inflammatory arthritis.
Fig. 5: Neutrophil-NPs ameliorate joint destruction and elicit a systemic therapeutic response following a prophylactic regimen.

Data availability

The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work is supported by the Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense under grant no. HDTRA1-14-1-0064 and National Science Foundation grant no. DMR-1505699.

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Lia.Z. conceived and designed the experiments with W.G. and Q.Z. Q.Z., X.C., D.D., Y.Z., J.Z. and Lia.Z. performed all experiments. All authors analysed and discussed the data. Q.Z., W.G., R.H.F. and Lia.Z. wrote the paper.

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Correspondence to Liangfang Zhang.

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Zhang, Q., Dehaini, D., Zhang, Y. et al. Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis. Nature Nanotech 13, 1182–1190 (2018). https://doi.org/10.1038/s41565-018-0254-4

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