fig4

Figure 4. In vivo joint-targeting and anti-arthritic effects of TWELP@GlcN-HA in CIA mice. (A) In vivo fluorescence imaging at 24, 48, and 72 h after tail-vein injection of Free DiR, TWELP-DiR, or TWELP@GlcN-HA-DiR, showing stronger and sustained signals at inflamed joints for TWELP@GlcN-HA-DiR; (B) Quantitative analysis of fluorescence intensity in the inflamed paws at 24, 48, and 72 h after tail-vein injection; (C) Timeline of CIA model establishment and treatment; (D-F) Body weight, clinical arthritis scores, and hind paw thickness over time; (G) Representative hind paw images at study endpoint (scale bar: 2 mm); (H) 3D micro-CT images of the right hind limb showing bone architecture and erosion (scale bar: 5 mm). Data are presented as mean ± SD (n = 4). Longitudinal data were analyzed using two-way repeated-measures ANOVA, with measurements from the same animal matched across time, followed by Sidak’s multiple comparisons test. ^*P < 0.05, ^**P < 0.01, and ^***P < 0.001. ANOVA: Analysis of variance; CIA: collagen-induced arthritis; DiR: 1,1’-dioctadecyl-3,3,3’,3’-tetramethylindotricarbocyanine iodide; GlcN: glucosamine; micro-CT: micro-computed tomography; SD: standard deviation; TP: triptolide; TWELP: Tripterygium wilfordii-derived exosome-like nanoparticles; TWELP-DiR: DiR-labeled TWELP; TWELP@GlcN-HA: engineered Tripterygium wilfordii-derived exosome-like nanoparticle system; TWELP@GlcN-HA-DiR: DiR-labeled TWELP@GlcN-HA; TWELP@HA: hyaluronic acid-modified TWELP.