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Research Article

Engineered protein and Jakinib nanoplatform with extraordinary rheumatoid arthritis treatment

Yuanxin Li1,2, Bo Li3, Gang Wang4, Juanjuan Su5, Yilin Qiao3, Chao Ma3, Fan Wang1, Jian Zhu6( ), Jingjing Li1( ), Hongjie Zhang1,3, Kai Liu3( ), Huji Xu4( )
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
University of Science and Technology of China, Hefei 230026, China
Engineering Research Center of Advanced Rare Earth Materials, (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China
School of Clinical Medicine, Tsinghua University, Beijing 100084, China
College of Materials Science and Opto-Electronic Technology, University of Chinese Academy of Sciences, Beijing 100049, China
First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
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Graphical Abstract

The protein nanoplatform of PCP-UPA (protein complex particle-upadacitinib) was designed and fabricated, which showed an ultralong half-life, higher bioavailability and enhanced pharmaceutical effect when compared with the commercial orally administrated upadacitinib.

Abstract

Rheumatoid arthritis (RA) is a relatively common inflammatory disease that affects the synovial tissue, eventually results in joints destruction and even long-term disability. Although Janus kinase inhibitors (Jakinibs) show a rapid efficacy and are becoming the most successful agents in RA therapy, high dosing at frequent interval and severe toxicities cannot be avoided. Here, we developed a new type of fully compatible nanocarriers based on recombinant chimeric proteins with outstanding controlled release of upadacitinib. In addition, the fluorescent protein component of the nanocarriers enabled noninvasive fluorescence imaging of RA lesions, thus allowing real-time detection of RA therapy. Using rat models, the nanotherapeutic is shown to be superior to free upadacitinib, as indicated by extended circulation time and sustained bioefficacy. Strikingly, this nanosystem possesses an ultralong half-life of 45 h and a bioavailability of 4-times higher than pristine upadacitinib, thus extending the dosing interval from one day to 2 weeks. Side effects such as over-immunosuppression and leukocyte levels reduction were significantly mitigated. This smart strategy boosts efficacy, safety and visuality of Jakinibs in RA therapy, and potently enables customized designs of nanoplatforms for other therapeutics.

Keywords

controlled releaserheumatoid arthritisnanocarrierengineered proteinbioefficacy

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Nano Research
Volume 16 Issue 8,
August 2023
Pages 11197-11205
DOI: 10.1007/s12274-023-5838-0
Cite this article:
Li Y, Li B, Wang G, et al. Engineered protein and Jakinib nanoplatform with extraordinary rheumatoid arthritis treatment. Nano Research, 2023, 16(8): 11197-11205. https://doi.org/10.1007/s12274-023-5838-0
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Received: 25 March 2023
Revised: 13 May 2023
Accepted: 15 May 2023
Published: 10 June 2023
© Tsinghua University Press 2023
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