Fig. 7: Treatment of LPS-induced systemic inflammation using VEDIC and VFIC-EV mediated delivery of a super-repressor of NF-ĸB.

a, b Design of the constructs and reporter cells utilized for delivery and assessment of a super-repressor of NF-ĸB by engineered EVs. c Schematic illustration how the EV-delivered super-repressor of NF-ĸB inhibits NF-ĸB activity. d, e Luciferase activity from HEK-NF-ĸB reporter cells, 24 or 48 h after treatment with engineered EVs (TNF-α stimulation for 6 h before harvesting cells), in 24-well plates. f Schematic illustration of the workflow for the treatment of LPS-induced systemic inflammation by engineered EVs in mice (5×10¹¹ EVs/mouse per dose). g, h Percentage of body weight loss and group survival in mice after LPS and engineered EV injections. n = 10 mice per group. i Representative histology images (hematoxylin-eosin stain) of liver to show the aggregation of inflammatory cells (upper panel, yellow arrows indicate the aggregated inflammatory cells in portal areas) and the hydropic degeneration of hepatocytes (lower panel, red arrows indicate the hydropic degeneration of hepatocytes) after LPS induction. Scale bar, 50 µm. j Accumulation of inflammatory cells in the proximal region of renal tubules as shown by the representative histology images (yellow arrows indicate the inflammatory cells). Scale bar, 50 µm. Two-way (Tukey) ANOVA multiple comparisons test was used for analysis of (d, e, and g); Log-rank (Mantel-Cox) test was used for the analysis of survival curve (h). Experiments were done with 8 biological replicates for (d and e) and data are shown as mean ± SD. c, f Created in BioRender.com, Zheng, W. (2025) https://BioRender.com/s30x956 and Zheng, W. (2025) https://BioRender.com/j46d117 respectively. Exact statistical analysis was reported in the Source data and Source data are provided as a Source Data file.