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Issue 11, 2019
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Nanoparticle-delivered siRNA targeting Bruton's tyrosine kinase for rheumatoid arthritis therapy

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Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease that can cause irreversible joint deformity. There is still no cure for RA, and current therapeutics, including methotrexate and adalimumab, cause serious off-target effects and systemic immunosuppression, which in turn increases the risk of infection. Bruton's tyrosine kinase (BTK) in macrophages and B cells has been demonstrated to be a promising therapeutic target for RA. However, high doses of BTK inhibitors are required for efficient BTK suppression, which limits their clinical use. Small interfering RNA (siRNA) is promising for the silencing of specific genes and has been used for the treatment of multiple diseases. To deliver siRNA into macrophages and B cells for BTK gene silencing, we employed cationic lipid-assisted PEG-b-PLGA nanoparticles (CLANs) to encapsulate siRNA. We demonstrated that macrophages and B cells were able to efficiently ingest the CLANs both in vitro and in vivo. Thereafter, we encapsulated siRNA targeting BTK (siBTK) into the CLANs, denoted as CLANsiBTK, and demonstrated that CLANsiBTK significantly inhibited BTK expression in macrophages and B cells. In a collagen-induced mouse arthritis model, CLANsiBTK treatment dramatically reduced joint inflammation and other RA symptoms but showed no toxicity, proving that using CLANsiBTK is a promising approach for RA therapy.

Graphical abstract: Nanoparticle-delivered siRNA targeting Bruton's tyrosine kinase for rheumatoid arthritis therapy

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Publication details

The article was received on 02 Jul 2019, accepted on 24 Aug 2019 and first published on 27 Aug 2019


Article type: Paper
DOI: 10.1039/C9BM01025D
Biomater. Sci., 2019,7, 4698-4707

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    Nanoparticle-delivered siRNA targeting Bruton's tyrosine kinase for rheumatoid arthritis therapy

    G. Zhao, A. Liu, Y. Zhang, Z. Zuo, Z. Cao, H. Zhang, C. Xu and J. Wang, Biomater. Sci., 2019, 7, 4698
    DOI: 10.1039/C9BM01025D

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