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Nano Research 2023, 16(7): 9781-9791 https://doi.org/10.1007/s12274-023-5646-6
Research Article | Issue | Published: 14 April 2023

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

Show Author's Information Shuilian Fu1,§,  Zhiting Cao3,§,  Baolian Huang3,§,  Te Yin3,  Chujun Huang1,  Zhiqian Bi1,  Yingying Yao1,  Xiaoyao Chang1,  Hongqin Zhuang1( ),  Zi-Chun Hua1,2,3( )
The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210023, China
Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou 213164, China
School of Biopharmacy, China Pharmaceutical University, Nanjing 211198, China

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

Keywords:
nanoparticles, allergic rhinitis, epithelial permeability, tumor necrosis factor-alpha (TNF-α) nanobody, tight junctions
Topics:
Drug deliveryDrug therapy
Cite this article:
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 Research, 2023, 16(7): 9781-9791. https://doi.org/10.1007/s12274-023-5646-6
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Abstract Full text Electronic supplementary material About this article

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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Electronic supplementary material
About this article

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

Show Author's information Shuilian Fu1,§, Zhiting Cao3,§, Baolian Huang3,§, Te Yin3, Chujun Huang1, Zhiqian Bi1, Yingying Yao1, Xiaoyao Chang1, Hongqin Zhuang1( ), Zi-Chun Hua1,2,3( )
The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210023, China
Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou 213164, China
School of Biopharmacy, China Pharmaceutical University, Nanjing 211198, China

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

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.

Keywords: nanoparticles, allergic rhinitis, epithelial permeability, tumor necrosis factor-alpha (TNF-α) nanobody, tight junctions

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Publication history
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Acknowledgements

Publication history

Received: 15 December 2022
Revised: 27 February 2023
Accepted: 07 March 2023
Published: 14 April 2023
Issue date: July 2023

Copyright

© Tsinghua University Press 2023

Acknowledgements

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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