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Research Article | Open Access

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

Le Jianga,b,Yifan Wanga,b,Chunlin Liua,b,Nan Xua,bWenshuo Lia,bLei WangcYixian Wua,bJingyun Wanga,bZhijun Hea,bFengbo Suna,bLingyun Zhaoa,bQiong WucXiumei Wanga,bHuihui 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.

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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.

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Journal of Advanced Ceramics
Pages 1105-1117
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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Received: 03 December 2022
Revised: 01 January 2023
Accepted: 04 February 2023
Published: 09 March 2023
© The Author(s) 2023.

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