Fig. 7: GEM/AZE–paclitaxome-2 synergistically boosted the antitumor efficacy in advanced KPC-Luc pancreas cancer mouse model with metastasis.
a, Drug CI of various molar ratios of GEM and SM–AZE–PTX in KPC-Luc cells by cytotoxicity test (n = 3 biological replicates per group). b,c, Schematic depicting the preparation (b) and cryoEM (c) of CD47p/GEM/AZE–paclitaxome-2, n = 3 samples per group were performed independently with similar results. d–f, Representative distribution of DLS size via intensity (d) and DLS size (e) and zeta potential (f) monitoring over a 15-day period at 4 °C of GEM/Lipo–SM, GEM/AZE–paclitaxome-2 and CD47p/GEM/AZE–paclitaxome-2 (n = 3 independent experiments per group). g–j, Blood kinetics (g,i) and tissue distribution (h,j) at 24 h in orthotopic KPC-Luc tumor mouse model (n = 3 mice per group, tumors ~400 mg) after an i.v. administration of free GEM, GEM/Lipo–SM, GEM/Lipo–SM + Abraxane or CD47p/GEM/AZE–paclitaxome-2 at 12.3 mg GEM kg−1 and 70 mg PTX kg−1. k–p, Antitumor effect in orthotopic PC mouse model with metastasis. B6129SF1/J mice were surgically inoculated with 2 × 106 cells into the pancreas (n = 5 mice per group). When the main tumor grew to ~400 mg with palpable metastasis (k), the animals were intravenously administered with GEM/Lipo–SM (12.3 mg kg−1), Abraxane (70 mg PTX kg−1), GEM/Lipo–SM + Abraxane (12.3 mg GEM kg−1, 70 mg PTX kg−1), CD47p/AZE–paclitaxome-2 (70 mg PTX kg−1), GEM/Lipo–SM + CD47p/AZE–paclitaxome-2 or CD47p/GEM/AZE–paclitaxome-2 at (MTD; Extended Data Fig. 7a) 12.3 mg GEM kg−1 and 70 mg PTX kg−1 (SM–AZE–PTX/GEM molar ratio of 2:1) on day 11 and 19. l, BLI of mice by Lago imaging from day 11, 18 to 25. On day 24, one mouse died from 5% dextrose group. m, On day 25, representative ex vivo BLI of different organs. n, The BLI of entire tumor burden in animal by normalization (red arrow indicates the time of drug injection). o,p, BLI of different organs by normalization (o) and metastatic frequency heatmap (p) on day 25. Data are presented as mean ± s.d. within a,e–j,n,o. One-way ANOVA with Tukey’s multiple comparisons test were used to calculate the exact P values in the statistical analyses
