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Bio-inspired nanoenzyme for metabolic reprogramming and anti-inflammatory treatment of hyperuricemia and gout

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Abstract

Gout, a common type of inflammatory arthritis resulting from chronic elevation of uric acid (UA) level, is usually accompanied with hyperuricemia. The current clinical drugs for the treatment of gout and hyperuricemia are greatly restricted by their limited therapeutic efficacy, off-target toxicity and severe side effects. Here, a neutrophil membrane (NM)-coated and cascade catalytic nanoenzyme was devised with excellent inflammation targeting, inflammatory cytokines neutralizing and UA degrading characteristics for the treatment of gout and hyperuricemia with high efficacy and safety. This nanoenzyme was fabricated by encapsulating uricase (UOx) and catalase (CAT) into zeolitic imidazolate framework-8 (ZIF-8) and further coating it with NM. The NM-coated nanoenzyme inherits the antigenic exterior and cell membrane functions of neutrophils for inflammation targeting and cytokine neutralization. UOx and CAT encapsulated in ZIF-8 could efficiently degrade UA and eliminate hydrogen peroxide (H2O2) via a biocatalytic cascade, thus successfully blocking the inflammation amplification during gout development. Both in vitro and in vivo experiments demonstrated the preferable potentials of the nanoenzyme for gout targeting, inflammation elimination and UA degradation, exhibiting great promise for the treatment of gout and hyperuricemia in an effective and safe manner.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (51833007, 51690152, 51988102, 21721005).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, China

    Lu Zhang, Chi Zhang, Ze-Nan Zhuang, Chu-Xin Li, Pei Pan, Cheng Zhang & Xian-Zheng Zhang

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  1. Lu Zhang
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  2. Chi Zhang
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  3. Ze-Nan Zhuang
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  4. Chu-Xin Li
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  5. Pei Pan
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  6. Cheng Zhang
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  7. Xian-Zheng Zhang
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Correspondence to Xian-Zheng Zhang.

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Zhang, L., Zhang, C., Zhuang, ZN. et al. Bio-inspired nanoenzyme for metabolic reprogramming and anti-inflammatory treatment of hyperuricemia and gout. Sci. China Chem. 64, 616–628 (2021). https://doi.org/10.1007/s11426-020-9923-9

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  • DOI: https://doi.org/10.1007/s11426-020-9923-9

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