Fig. 5

Increased drug infiltration to GBM by inhibiting astrocytic scar formation. a i) Schematic illustrating the limited chemo-drug infiltration to GBM region due to the astrocytic scar barrier. ii) Timeline for assessing drug infiltration to GBM with scar inhibition in vitro. b, d Fluorescent images and quantitative results for the intensity of fluorescein sodium salt (NaFI, MW 376 Da), representing the increased infiltration of small molecular to GBM region induced by the scar inhibition. c, e Fluorescent images and quantitative results of GBM spheroid area, representing decreased sensitivity to TMZ treatment by the glial scar. Without the glial scar, GBM spheroids reduced their area after TMZ treatment (D10) compared to that of before treatment (D4) (GBM + TMZ). With the glial scar, no significant reduction in GBM spheroid area were observed after treatment with TMZ (GBM MG AC + TMZ). f Increased sensitivity to TMZ with scar inhibition by TBOA and KDS2010 in vitro. g Ex vivo images representing the increased DOX penetration after scar inhibition (n = 2). h Experimental protocol for assessing drug sensitivity with scar inhibition in vivo. i-j Bioluminescence images and quantification of GBM tumor upon TMZ treatment with scar inhibition by TBOA and KDS2010 (n = 5). k Survival rate of mice (n = 5. Data were presented as means ± SD (n = 3, unless otherwise noted), except data in 5j which was presented in means ± SEM. *, p < 0.05; **, p < 0.01; ****, p < 0.0001. p values were calculated by two-tailed unpaired Student’s t-test for comparisons between two groups, and by one-way ANOVA for multiple comparisons. Differences in survival rate was tested by log-rank (Mantel-Cox) test. DOX, Doxorubicin; TMZ, Temozolomide. Scale bars represent 200 μm