Dual-targeted halofuginone hydrobromide nanocomplexes for promotion of macrophage repolarization and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes in adjuvant-induced arthritis in rats
10.1016/j.jpha.2024.100981
- Author:
Junping ZHU
1
;
Ye LIN
;
Gejing LI
;
Yini HE
;
Zhaoli SU
;
Yuanyuan TANG
;
Ye ZHANG
;
Qian XU
;
Zhongliu YAO
;
Hua ZHOU
;
Bin LIU
;
Xiong CAI
Author Information
1. Institute of Innovation and Applied Research in Chinese Medicine;Department of Rheumatology of First Hospital,Hunan University of Chinese Medicine,Changsha,410208,China
- Publication Type:Journal Article
- Keywords:
Halofuginone hydrobromide;
Rheumatoid arthritis;
Nanocomplexes;
Macrophage polarization;
Rheumatoid arthritis fibroblast-like;
synoviocytes;
Adjuvant-induced arthritis
- From:
Journal of Pharmaceutical Analysis
2024;14(11):1625-1644
- CountryChina
- Language:English
-
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 inflam-mation 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(ti/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 inflam-mation 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.
