Citation: Chunlei Dai, Liying Wang, Xinru You, Yi Zhao, Zhong Cao, Jun Wu. Coffee-derived self-anti-inflammatory polymer as drug nanocarrier for enhanced rheumatoid arthritis treatment[J]. Chinese Chemical Letters, ;2025, 36(3): 109869. doi: 10.1016/j.cclet.2024.109869 shu

Coffee-derived self-anti-inflammatory polymer as drug nanocarrier for enhanced rheumatoid arthritis treatment

Chunlei Dai ^a ,
Liying Wang ^a ,
Xinru You ^c ,
Yi Zhao ^{a, *,} ,
Zhong Cao ^{a, f, *,} ,
Jun Wu ^{b, d, e, *,}

a.
School of Biomedical Engineering, Sun Yat-sen University, Shenzhen 518107, China
b.
RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
c.
Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States
d.
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Nansha, Guangzhou 511400, China
e.
Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR, China
f.
Shenzhen International Institute for Biomedical Research, Shenzhen 518116, China

zhaoy529@mail.sysu.edu.cn

caozhong@mail.sysu.edu.cn

junwuhkust@ust.hk

Received Date: 3 March 2024
Revised Date: 2 April 2024
Accepted Date: 7 April 2024
Available Online: 8 April 2024

Figures(8)

Systemic administration of the anti-rheumatic drug methotrexate (MTX) for a long period of time may lead to therapeutic tolerance, various adverse effects, and potential harm to the immune system. Therapeutic nano-delivery carriers constructed based on biologically active phenols provide a promising approach to enhance the therapeutic effect of anti-rheumatic drugs. Caffeic acid, a natural compound with anti-inflammatory properties, holds significant potential in the treatment of diverse inflammatory conditions. In this paper, we first constructed a nano-delivery platform for MTX using caffeic acid-based polyphenol polymer Ph-CaA-OH (PCOH), and investigated the treatment of rheumatoid arthritis (RA) at low drug administration doses (2.5 mg/kg). PCOH nanoparticles (NPs) could inhibit lipopolysaccharidesstimulated macrophage inducible nitric oxide synthase (iNOS) expression and pro-inflammatory differentiation in vitro. In vivo imaging revealed the rapid accumulation and sustained presence of PCOH NPs at inflamed joints in collagen induced-arthritis (CIA) mice. Therapeutic evaluation of CIA mice demonstrated that MTX@PCOH NPs were superior to free MTX in reducing the progression of RA and decreasing the expression of multiple pro-inflammatory cytokines without significant toxic effects. By enhancing drug aggregation at inflammatory joints and capitalizing on the synergistic effects of active carriers, MTX@PCOH NPs effectively minimized the required drug dosage and mitigated toxic side effects in RA treatment. The application of PCOH NPs to RA treatment provides a new strategy for the development of safer and more effective anti-RA nanomedicines.
- Rheumatoid arthritis,
- Caffeic acid,
- Self-anti-inflammatory polymer,
- Nanocarrier,
- Methotrexate
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