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. 2023 Jun 10:1–9. Online ahead of print. doi: 10.1007/s12274-023-5838-0

Engineered protein and Jakinib nanoplatform with extraordinary rheumatoid arthritis treatment

Yuanxin Li 1,2, Bo Li 3, Gang Wang 4, Juanjuan Su 5, Yilin Qiao 3, Chao Ma 3, Fan Wang 1, Jian Zhu 6,✉, Jingjing Li 1,✉, Hongjie Zhang 1,3, Kai Liu 3,✉, Huji Xu 4,✉
PMCID: PMC10256963  PMID: 37359076

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. graphic file with name 12274_2023_5838_Fig1_HTML.jpg

Electronic Supplementary Material

Supplementary material (further details of DLS analysis, biocompatibility of PCP-UPA, CIA models construction, etc.) is available in the online version of this article at 10.1007/s12274-023-5838-0.

Keywords: engineered protein, nanocarrier, controlled release, bioefficacy, rheumatoid arthritis

Electronic Supplementary Material

12274_2023_5838_MOESM1_ESM.pdf (1.8MB, pdf)

Engineered protein and Jakinib nanoplatform with extraordinary rheumatoid arthritis treatment

Acknowledgements

This research was supported by the National Key R&D Program of China (Nos. 2022YFA0913200, 2021YFF0701800, 2022YFF0710000, and 2020YFA0908900), the National Natural Science Foundation of China (Nos. 22107097, 22020102003, 22277064, 82272161, and 22125701), Tsinghua University Spring Breeze Fund grant (No. 2021Z99CFZ005), and the Youth Innovation Promotion Association of CAS (No. 2021226) All animal experiments were conducted in compliance with the Animal Management Rules of the Ministry of Health of the People’s Republic of China, and with the approval of the Institutional Animal Care and Use Committee of the Animal Experiment Center of Jilin University (No. PZPX20180929070).

Contributor Information

Jian Zhu, Email: jian_jzhu@126.com.

Jingjing Li, Email: jjingli@ciac.ac.cn.

Kai Liu, Email: kailiu@tsinghua.edu.cn.

Huji Xu, Email: huji_xu@tsinghua.edu.cn.

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Supplementary Materials

12274_2023_5838_MOESM1_ESM.pdf (1.8MB, pdf)

Engineered protein and Jakinib nanoplatform with extraordinary rheumatoid arthritis treatment

Articles from Nano Research are provided here courtesy of Nature Publishing Group

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