a–c Four hours after IV injection, RNAs were purified from livers (n = 5 animals per group). Relative expression of IFN-β (a), CXCL9 (b), and CXCL10 (c) genes was measured by RT-qPCR, normalized against the housekeeping gene RPS13. d–f Orthotopic hepatocellular carcinoma was induced by injecting 1.5 × 106 Hepa1–6 cells into spleen. Unloaded EVs, CDN2 (0.2 μg), and exoCDN2 (0.2 μg) were injected intravenously at Day 4, 7, and 10 after cell injection (n = 8 animals per group). At Day 15, mice were sacrificed, and livers were collected. Liver weight (LW) over body weight (BW) was calculated (d) and % lesions scores were evaluated (e). Representative liver images were taken (f). Data are presented as means ± s.e.m from replicate samples as indicated. *P < 0.05; ****P < 0.0001 by one-way ANOVA with Tukey’s multiple comparison test.