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.