Fig. 8: CBPt/AZE–paclitaxome-2 significantly reduced tumor growth in a postsurgical tumor relapse 4T1-Luc2 TNBC model.
a, Drug CI of various molar ratios of CBPt and SM–AZE-PTX in 4T1-Luc2 cells by cytotoxicity test (n = 3 biological replicates per group). b,c, Schematic depicting the preparation (b), and cryoEM (c) of CD47p/CBPt/AZE–paclitaxome-2, n = 3 samples per group were performed independently with similar results. d–f, The representative distribution of DLS size via intensity (d), DLS size (e) and zeta potential (f) monitoring over a 15-day period at 4 °C of CBPt/Lipo–SM, CBPt/AZE–paclitaxome-2 and CD47p/CBPt/AZE–paclitaxome-2 (n = 3 independent experiments per group). g–i, Blood kinetics (g,i) and tissue distribution (h,j) at 24 h in orthotopic 4T1-Luc2 tumor mouse model (n = 3 mice per group, tumors ~400 mm3) after an i.v. administration of free CBPt, CBPt/Lipo–SM, CBPt/Lipo–SM + Abraxane or CD47p/CBPt/AZE–paclitaxome-2 at 7.6 mg CBPt kg−1 and 70 mg PTX kg−1 (SM–AZE–PTX/CBPt molar ratio of 4:1). k–p, 19 days after Balb/c mice were surgically inoculated with 1 × 105 4T1 cells at fourth mammary gland fat pad (n = 5 mice per group, tumor size ~400 mm3), the main tumors were removed and animal were i.v. administered with CBPt/Lipo–SM (7.6 mg kg−1), Taxol (20 mg PTX kg−1, MTD), PTX/Lipo–SM (40 mg PTX kg−1, MTD), Abraxane, CBPt/Lipo–SM + Abraxane, AZE–paclitaxome-2, CBPt/AZE–paclitaxome-2 or CD47p/CBPt/AZE–paclitaxome-2 at a dose of 7.6 mg CBPt kg−1 and 70 mg PTX kg−1 on day 20 and 28. k, Animal BLI before and after surgery. Red circle indicates tumor-free mice. l, Metastatic BLI of lung in mice ex vivo on day 48. m, Tumor growth plots, (red arrow indicates drug injection). n, Intratumoral platinum–DNA adducts from m on day 48. o, Quantification of BLI for lung metastasis from l via Lago optical imaging. p, Kaplan–Meier survival plots from a separate study in which mice received the same treatments as m. Data are presented as mean ± s.d. (a,e–j,m–o). One-way ANOVA with Tukey’s multiple comparisons test were used to calculate the exact P values and a log-rank Mantel–Cox test was utilized to compare the survival plot in the statistical analyses.
