Fig. 6

In vivo delivery of miR-34a via nanocells sensitizes to TMZ. a–c Intravenously-administered nanocells deliver miR-34a to orthotopically implanted tumors. Five hundred thousand GBM6 cells expressing firefly luciferase were implanted in the striatum of female athymic nude mice. Six mice were used in each group. Three doses of 10⁹ nanocells packaging either miR-34a or control miRNA were injected intravenously on days 30, 31 and 32 post-tumor implantation and tumors were harvested day 35 post implantation for analysis of cMet mRNA expression by RT-qPCR (b) and phospho-Akt levels by western blotting (c). Data represent mean relative expression (± SD); a paired t-test was used to test for significant difference between means, *p < 0.05. d–g miR-34a inhibits tumor growth, improves survival and sensitizes to TMZ. Six mice were used in each experimental group. Tumor cell implantation was carried out as described under (a–c). Three doses of 10⁹ nanocells packaging either miR-34a or control miRNA were injected intravenously on days 31, 33 and 35 and TMZ was administered via oral gavage on days 34, 35, 36, 37 and 38 post-tumor implantation. (e) Tumor growth was monitored by bioluminescence imaging. Data represents mean total flux (± SD) and a paired t-test was used to test for significant difference between means; *p < 0.05. (f) Representative bioluminescent imaging from Day 43 post tumor implantation. (g) Survival of mice shown as Kaplan–Meier survival curves. Log rank test was used to assess statistical significance, (n = 6); *p < 0.05 and #p < 0.001 vs control nanocell-treated mice