Fig. 3: E8 biodistribution and efficacy in an animal model.

a E8, modified with Cy5.5 and PEG, was injected at 6 or 60 mg/kg, i.v. into NOD/SCID mice bearing MDA-MB-231-derived tumors on their right hind limb. Fluorescence was measured in vivo immediately after injection and following 24 and 48 h. White arrows point to tumor locations. Color scales are indicated on the right; left scale relates to 6 mg/kg, right scale to 60 mg/kg. b Homing and retention of E8 at tumor site 3 h following i.v. injection (Ve, vehicle; K, kidney). Inset region is shown magnified on the right. White arrowhead points to tumor site. c Quantitative measurement of E8 level in tumors up to 48 h post injection. E8 level peaks at 1–3 h post injection, then fall but is still maintained later. d The efficacy of E8 in mice bearing MDA-MB-231-derived tumors. E8 was injected at 100 mg/kg, 1 dose/2 d for 11 d, and tumor volumes were measured. Mean tumor volumes of the two groups are statistically indifferent at day 0. Asterisks denote a statistically significant difference with p < 0.05 (n = 8 mice/group). Ve, vehicle. Seq, control oligo. e Representative photographs of tumors excised from mice sacrificed at day 11. Tumors from E8-treated mice appear necrotic. Scale bars, 5 mm. f, g histochemical analysis of caspase-3 activity in tumor-derived tissue sections (f, vehicle-treated; g, E8-treated). Caspase-3 activity is exhibited as brown color. Scale bar, 500 μM. h, i TUNEL analysis of tumor-derived tissue sections (h, vehicle-treated; i, E8-treated). See Supplementary Fig. 18 for a magnified version of these panels. Scale bar, 500 μM.