Extended Data Fig. 6: CD47p/AZE-Paclitaxome-2 outperformed CP–PTX and PGG–PTX in drug delivery and antitumor efficacy in metastatic orthotopic KPC-Luc PC mouse model.
a-c, Blood kinetics (a), tissue distribution (b) at 24 h in orthotopic KPC-Luc tumor mouse model (n = 3 mice per group, tumors ~400 mg). Animals were intravenously administered once with CP–PTX, PGG–PTX, Paclitaxome-2, AZE-Paclitaxome-2 and CD47p/AZE-Paclitaxome-2 at 70 mg PTX/kg, respectively. HPLC was used to determine the drug levels in primary organs and plasma. c, Representative images of extravasation and penetration for Cy5/CP–PTX and Cy5/PGG–PTX within the tumors by using CLSM (n = 3 tumors per group). DSPE–Cy5 were used to label CP–PTX and PGG–PTX, twenty-four hours after injecting Cy5/CP–PTX and Cy5/PGG–PTX (red) at e.q. 0.84 mg DSPE–Cy5 and 70 mg PTX/kg (n = 3 mice per group, tumors: ~400 mg), CLSM of slices of KPC-Luc tumor was performed. DAPI (blue) was utilized to stain cell nuclei. Primary antibody for PECAM1 first and then Alexa FluorTM 488 detection antibody (green) were used to label the vessels of blood. Scale bars, 50 μm. d-i, B6129SF1/J mice were surgically inoculated with 2 × 106 KPC-Luc cells into their pancreas (n = 5 mice per group). When the main tumor grew to ~400 mg and had discernible metastasis on day 10, the animals were administered intravenously with CP–PTX, PGG–PTX, Paclitaxome-2, AZE-Paclitaxome-2, CD47p/AZE-Paclitaxome-2, at eq. 70 mg PTX/kg on day 10 and 18. d, BLI of mice by Lago imaging on day 10, 17 and 24. e, On day 24, representative ex vivo BLI for different organs. f, The BLI of entire tumor burden in animal by normalization (red arrow: time of drug injection). BLI of different organs by normalization (g) and metastatic frequency heatmap (h) on day 24. i, Representative intratumoral IHC staining for CC-3, (scale bar: 100 μm), and immunofluorescence staining for β-tubulin (scale bar: 50 μm). Data are presented as average ± s.d. within a, b, f and g. One-way ANOVA with Tukey’s multiple comparisons test were used to calculate the exact P values in the statistical analyses.
