Dual-targeted halofuginone hydrobromide nanocomplexes for promotion of macrophage repolarization and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes in adjuvant-induced arthritis in rats

Junping Zhu; Ye Lin; Gejing Li; Yini He; Zhaoli Su; Yuanyuan Tang; Ye Zhang; Qian Xu; Zhongliu Yao; Hua Zhou; Bin Liu; Xiong Cai

doi:10.1016/j.jpha.2024.100981

Volume 14 Issue 11

Nov. 2024

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Junping Zhu, Ye Lin, Gejing Li, Yini He, Zhaoli Su, Yuanyuan Tang, Ye Zhang, Qian Xu, Zhongliu Yao, Hua Zhou, Bin Liu, Xiong Cai. Dual-targeted halofuginone hydrobromide nanocomplexes for promotion of macrophage repolarization and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes in adjuvant-induced arthritis in rats[J]. Journal of Pharmaceutical Analysis, 2024, 14(11): 100981. doi: 10.1016/j.jpha.2024.100981

Citation:

Junping Zhu, Ye Lin, Gejing Li, Yini He, Zhaoli Su, Yuanyuan Tang, Ye Zhang, Qian Xu, Zhongliu Yao, Hua Zhou, Bin Liu, Xiong Cai. Dual-targeted halofuginone hydrobromide nanocomplexes for promotion of macrophage repolarization and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes in adjuvant-induced arthritis in rats[J]. Journal of Pharmaceutical Analysis, 2024, 14(11): 100981. doi: 10.1016/j.jpha.2024.100981

Citation:

Junping Zhu, Ye Lin, Gejing Li, Yini He, Zhaoli Su, Yuanyuan Tang, Ye Zhang, Qian Xu, Zhongliu Yao, Hua Zhou, Bin Liu, Xiong Cai. Dual-targeted halofuginone hydrobromide nanocomplexes for promotion of macrophage repolarization and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes in adjuvant-induced arthritis in rats[J]. Journal of Pharmaceutical Analysis, 2024, 14(11): 100981. doi: 10.1016/j.jpha.2024.100981

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Dual-targeted halofuginone hydrobromide nanocomplexes for promotion of macrophage repolarization and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes in adjuvant-induced arthritis in rats

doi: 10.1016/j.jpha.2024.100981

Junping Zhu^a,
Ye Lin^a,
Gejing Li^a,
Yini He^a,
Zhaoli Su^a,
Yuanyuan Tang^a,b,
Ye Zhang^a,
Qian Xu^a,
Zhongliu Yao^a,
Hua Zhou^{c
,
,},
Bin Liu^{b
,
,},
Xiong Cai^{a
,
,}

a. Institute of Innovation and Applied Research in Chinese Medicine;
Department of Rheumatology of First Hospital, Hunan University of Chinese Medicine, Changsha, 410208, China;
b. College of Biology, Hunan University, Changsha, 410082, China;
c. State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

Funds:

This work was funded by grants from the National Natural Science Foundation of China (Grant No.: 82274506), the China Postdoctoral Science Foundation (Grant No.: 2022M721128), the Science and Technology Innovation Program of Hunan, China (Grant No.: 2021RC4035), the Natural Science Foundation of Hunan, China (Grant No.: 2023JJ40477), and the Open-competing Disciple Construction Project of Hunan University of Chinese Medicine (HNUCM), China (Grant No.: 22JBZ003), and was financially supported by the Furong Distinguished Scholar Program of Hunan, China (Program No.: XJT[2020]58), the 121 Training Project for Innovative Talents of Hunan, China (Project No.: XRSH[2019]192), the Chinese Academy of Engineering Academician Liang Liu's Workstation Project, China (Project No.: KH[2023]3-23YS001), and the World First-class Discipline Incubation Project of HNUCM, China (Project No.: XJF[2022]57).

Received Date: Jan. 09, 2024
Accepted Date: Apr. 18, 2024
Rev Recd Date: Apr. 16, 2024
Publish Date: Apr. 22, 2024

Abstract

Abstract

Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium. Currently, treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia. However, these modalities are unsatisfactory in achieving the desired therapeutic outcomes. Halofuginone hydrobromide (HF), an herbal active ingredient, has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation. However, HF's medical efficacy is limited due to its poor water solubility, short half-life (t_1/2), and non-target toxicity. In the current study, by using the advantages of nanotechnology, we presented a novel dual-targeted nanocomplex, termed HA-M@P@HF NPs, which consisted of a hyaluronic acid (HA)-modified hybrid membrane (M)-camouflaged poly lactic-co-glycolic acid (PLGA) nanosystem for HF delivery. These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA (HFLS-RA). In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia, safeguarding against bone destruction in rats with adjuvant-induced arthritis (AIA). Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA, thereby offering a promising therapeutic strategy for RA.
- Halofuginone hydrobromide,
- Rheumatoid arthritis,
- Nanocomplexes,
- Macrophage polarization,
- Rheumatoid arthritis fibroblast-like synoviocytes,
- Adjuvant-induced arthritis

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References(44)

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