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Journal of Advanced Ceramics 2023, 12(5): 1105-1117 https://doi.org/10.26599/JAC.2023.9220730
Research Article | Open Access | Issue | Published: 09 March 2023

Ultrasound-driven BaTiO3 nanorobots patching immunologic barrier to cure chronic rheumatoid arthritis

Show Author's Information Le Jianga,b,†,  Yifan Wanga,b,†,  Chunlin Liua,b,†,  Nan Xua,b,  Wenshuo Lia,b,  Lei Wangc,  Yixian Wua,b,  Jingyun Wanga,b,  Zhijun Hea,b,  Fengbo Suna,b,  Lingyun Zhaoa,b,  Qiong Wuc,  Xiumei Wanga,b,  Huihui Yuand( ),  Xiaohui Wanga,b( ),  Xiaodan Suna,b( )
State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China
Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China
MOE Key Lab. Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China
Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

† Le Jiang, Yifan Wang, and Chunlin Liu contributed equally to this work.

Keywords:
ultrasound-driven, BaTiO3 nanorobots (BTO NRs), immunologic barrier, upstream driver, rheumatoid arthritis (RA)
Cite this article:
Jiang L, Wang Y, Liu C, et al. Ultrasound-driven BaTiO3 nanorobots patching immunologic barrier to cure chronic rheumatoid arthritis. Journal of Advanced Ceramics, 2023, 12(5): 1105-1117. https://doi.org/10.26599/JAC.2023.9220730
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Abstract Full text Electronic supplementary material About this article

The disruption and reconstruction of the TREM2+ tissue resident macrophage (TRM) barrier on the surface of synovial lining play a key role in the activation and "remission" of rheumatoid arthritis (RA), which engender the prediction of this immunologic barrier as a potential driver for the achievement of "cure" in RA. However, strategies to promote the reconstruction of this barrier have not been reported, and the effect of patching this barrier remains unidentified. On the other hand, appropriate piezoelectric stimulation can reprogram macrophages, which has never been exerted on this barrier TRM yet. Herein, we design piezoelectric tetragonal BaTiO3 (BTO) ultrasound-driven nanorobots (USNRs) by the solvothermal synthesis method, which demonstrates satisfactory electro-mechanical conversion effects, paving the way to generate controllable electrical stimulation under ultrasound to reprogram the barrier TRM by minimally invasive injection into joint cavity. It is demonstrated that the immunologic barrier could be patched by this USNR effectively, thereby eliminating the hyperplasia of vessels and nerves (HVN) and synovitis. Additionally, TREM2 deficiency serum-transfected arthritis (STA) mice models are applied and proved the indispensable role of TREM2 in RA curing mediated by USNR. In all, our work is an interesting and important exploration to expand the classical tetragonal BTO nanoparticles in the treatment of autoimmune diseases, providing a new idea and direction for the biomedical application of piezoelectric ceramics.


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Abstract
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Electronic supplementary material
About this article

Ultrasound-driven BaTiO3 nanorobots patching immunologic barrier to cure chronic rheumatoid arthritis

Show Author's information Le Jianga,b,†, Yifan Wanga,b,†, Chunlin Liua,b,†, Nan Xua,b, Wenshuo Lia,b, Lei Wangc, Yixian Wua,b, Jingyun Wanga,b, Zhijun Hea,b, Fengbo Suna,b, Lingyun Zhaoa,b, Qiong Wuc, Xiumei Wanga,b, Huihui Yuand( ), Xiaohui Wanga,b( ), Xiaodan Suna,b( )
State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China
Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China
MOE Key Lab. Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China
Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

† Le Jiang, Yifan Wang, and Chunlin Liu contributed equally to this work.

Abstract

The disruption and reconstruction of the TREM2+ tissue resident macrophage (TRM) barrier on the surface of synovial lining play a key role in the activation and "remission" of rheumatoid arthritis (RA), which engender the prediction of this immunologic barrier as a potential driver for the achievement of "cure" in RA. However, strategies to promote the reconstruction of this barrier have not been reported, and the effect of patching this barrier remains unidentified. On the other hand, appropriate piezoelectric stimulation can reprogram macrophages, which has never been exerted on this barrier TRM yet. Herein, we design piezoelectric tetragonal BaTiO3 (BTO) ultrasound-driven nanorobots (USNRs) by the solvothermal synthesis method, which demonstrates satisfactory electro-mechanical conversion effects, paving the way to generate controllable electrical stimulation under ultrasound to reprogram the barrier TRM by minimally invasive injection into joint cavity. It is demonstrated that the immunologic barrier could be patched by this USNR effectively, thereby eliminating the hyperplasia of vessels and nerves (HVN) and synovitis. Additionally, TREM2 deficiency serum-transfected arthritis (STA) mice models are applied and proved the indispensable role of TREM2 in RA curing mediated by USNR. In all, our work is an interesting and important exploration to expand the classical tetragonal BTO nanoparticles in the treatment of autoimmune diseases, providing a new idea and direction for the biomedical application of piezoelectric ceramics.

Keywords: ultrasound-driven, BaTiO3 nanorobots (BTO NRs), immunologic barrier, upstream driver, rheumatoid arthritis (RA)

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Publication history

Received: 03 December 2022
Revised: 01 January 2023
Accepted: 04 February 2023
Published: 09 March 2023
Issue date: May 2023

Copyright

© The Author(s) 2023.

Acknowledgements

The authors would like to acknowledge the assistance of Yanli Zhang, Imaging Core Facility, Technology Center for Protein Sciences, Tsinghua University, for the assistance of using the spinning disk confocal microscopy (Dragonfly, Andor); Yue Sun, Center of Biomedical Analysis, Tsinghua University, for the assistance of using the automatic digital slide scanning system (Axio Scan. Z1, Zeiss); Jingjing Wang, Center of Biomedical Analysis, Tsinghua University, for the assistance of using the microscopy slide scanner (Pannoramic SCAN, 3D HISTECH); Prof. Christophe Benoist, Harvard University, for his generous donation of KRN mice; and Prof. Xin Lin, Department of Immunology, Tsinghua University, for his generous donation of TREM2 KO mice.

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