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Bioinspired metal-organic framework nanozyme reinforced with thermosensitive hydrogel for regulating inflammatory responses in Parkinson’s disease

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Abstract

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder accompanied by movement disorders and neuroinflammatory injury. Anti-inflammatory intervention to regulate oxidative stress in the brain is beneficial for managing PD. However, traditional natural antioxidants have failed to meet the clinical treatment demands due to insufficient activity and sustainability. Herein, Cu-doping zeolite imidazolate framework-8 (ZIF-8) nanozyme is designed to simulate Cu/Zn superoxide dismutase (SOD) by biomimetic mineralization. The nanozyme composite is then integrated into thermosensitive hydrogel (poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA)) to form an effective antioxidant system (Cu-ZIF@Hydrogel). The thermosensitive hydrogel incorporating nanozymes demonstrate distinct viscoelastic properties aimed at enhancing local nanozyme adhesion, prolonging nanozyme retention time, and modulating antioxidant activity, thus significantly improving the bioavailability of nanozymes. At the cellular and animal levels of PD, we find that Cu-ZIF@Hydrogel bypass the blood-brain barrier and efficiently accumulate in the nerve cells. Moreover, the Cu-ZIF@Hydrogel significantly alleviate the PD’s behavioral and pathological symptoms by reducing the neuroinflammatory levels in the lesion site. Therefore, the hydrogel-incorporating nanozyme system holds great potential as a simple and reliable avenue for managing PD.

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Acknowledgments

We are grateful for the financial support by the CAS Interdisciplinary Innovation Team (No. JCTD-2020-08).

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Author notes

  1. Xiaowan Fan, Tao Zhang, and Xin Ding contributed equally to this work.

Authors and Affiliations

  1. Nanozyme Medical Center, Academy of Medical Science, Zhengzhou University, Zhengzhou, 450001, China

    Xiaowan Fan, Yushuo Gu, Qing Li & Wei Jiang

  2. Department, Central-China Branch of National Center for Cardiovascular Diseases, Hean Cardiovascular Disease Center, Fuwai Central-China Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, 450046, China

    Wei Jiang

  3. Application Center for Precision Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Xiaowan Fan, Yushuo Gu, Qing Li, Wei Jiang & Kelong Fan

  4. CAS Engineering Laboratory for Nanozyme, Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Kelong Fan

  5. University of Chinese Academy of Sciences, Beijing, 101408, China

    Kelong Fan

  6. Department of General Surgery, Strategic Support Force Medical Center, Beijing, 100101, China

    Tao Zhang

  7. Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Xin Ding

Authors
  1. Xiaowan Fan
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  2. Tao Zhang
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  3. Xin Ding
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  4. Yushuo Gu
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  5. Qing Li
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  6. Wei Jiang
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  7. Kelong Fan
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Corresponding authors

Correspondence to Qing Li, Wei Jiang or Kelong Fan.

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Bioinspired metal-organic framework nanozyme reinforced with thermosensitive hydrogel for regulating inflammatory responses in Parkinson’s disease

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Fan, X., Zhang, T., Ding, X. et al. Bioinspired metal-organic framework nanozyme reinforced with thermosensitive hydrogel for regulating inflammatory responses in Parkinson’s disease. Nano Res. 17, 858–865 (2024). https://doi.org/10.1007/s12274-023-6304-8

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  • DOI: https://doi.org/10.1007/s12274-023-6304-8

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