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Tannic acid assisted anti-TNF-α nanobody assembly modulating the epithelial barrier dysregulation of allergic rhinitis

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Abstract

The derailed nasal epithelial barrier is associated with the disorder of tight junctions (TJ) function or expression, leading to more penetration of allergens to the barrier, accompanied by the release of cytokines, which develop allergic rhinitis (AR). Considering the increasing AR disease incidence worldwide, there is still an urgent unmet medical need to develop new therapeutics. Tumor necrosis factor-alpha (TNF-α) inhibitors have been applied in treating autoimmune diseases. However, their roles in AR remain unclear. In this study, anti-TNF-α nanobody (V) was assembled with tannic acid (V/TA) as a functional antibody drug candidate which could inhibit the release of the cytokines in ovalbumin (OVA)-induced AR murine model. Upon receiving V/TA treatment, the infiltration level of inflammatory cells, and the number of mucus-secreting cells and mast cells in the nasal mucosa recovered to a relatively normal level. Preliminary mechanism of action research revealed that the efficacy of V/TA was accompanied by the restricted level of TJ molecules: zonula occluden-1 (ZO-1), occludin, claudin-1, and claudin-5. The therapeutic effect of the anti-TNF-α nanobody against AR was enhanced with the tannic acid assisted without any toxicity observed. This study supplied a promising delivery strategy of TNF-α inhibitor for the effective treatment of complicated allergic rhinitis disease, with an advantage in restoring effect on the AR-caused epithelial barrier defects than the commercial drug Infliximab.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (Nos. 82130106 and 32250016), Nanjing Special Fund for Life and Health Science and Technology (No. 202110016), and Changzhou Municipal Department of Science and Technology (Nos. CZ20210010, CJ20210024, and CJ20220019).

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  1. Shuilian Fu, Zhiting Cao, and Baolian Huang contributed equally to this work.

Authors and Affiliations

  1. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, 210023, China

    Shuilian Fu, Chujun Huang, Zhiqian Bi, Yingying Yao, Xiaoyao Chang, Hongqin Zhuang & Zi-Chun Hua

  2. Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou, 213164, China

    Zi-Chun Hua

  3. School of Biopharmacy, China Pharmaceutical University, Nanjing, 211198, China

    Zhiting Cao, Baolian Huang, Te Yin & Zi-Chun Hua

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  1. Shuilian Fu
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Correspondence to Hongqin Zhuang or Zi-Chun Hua.

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Fu, S., Cao, Z., Huang, B. et al. Tannic acid assisted anti-TNF-α nanobody assembly modulating the epithelial barrier dysregulation of allergic rhinitis. Nano Res. 16, 9781–9791 (2023). https://doi.org/10.1007/s12274-023-5646-6

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  • DOI: https://doi.org/10.1007/s12274-023-5646-6

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