Fig. 2: Paclitaxome-2 bolstered the maximum tolerated dose, reduced adverse effects and outperformed Taxol and Abraxane on therapeutic efficacy in an orthotopic 4T1 TNBC model.
a–h, MTD study of Taxol, PTX/Lipo–SM and three paclitaxomes in healthy Balb/c mice (n = 3 mice per group). The different PTX formulations were administered intravenously once from caudal vein, the survival and weight of the mouse were measured for 14 days. The maximum dose which did not trigger mortality or more than 15% of weight loss over the entire period was identified as MTD. The mouse weight measuring in MTD study of paclitaxome-1, paclitaxome-2 and paclitaxome-3 with different dose in healthy Balb/c mice (a), erythrocytes (b), leukocytes (c), serum chemistry (d), thrombocytes (e), the total number of dark cytoplasm (f) and vacuolations (g) in the whole cross-sectional area of dorsal root ganglia, and representative hematoxylin and eosin (H&E) staining for sternum and toluidine blue staining for dorsal root ganglia (h, red arrow indicates dark cytoplasm; yellow arrow indicates vacuolations. Scale bars, 100 μm (top) and 30 µm (bottom) at day 14 for the MTD groups. The whole cross-sectional area was full scanned by the Leica Aperio Versa 200 (Leica), the total number of dark cytoplasm and vacuolations in the panoramic images of dorsal root ganglia were analyzed by Aperio ImageScope software. i–k, Balb/c mice were surgically inoculated with 1 × 105 4T1 cells at the fourth mammary fat pad and on day 9 when tumors grew to ~100 mm3, animal (n = 5 mice per group) administered with equivalent (eq.) 20 mg PTX kg−1 on day 9 and 19 via intravenous (i.v.) injection, respectively. Average tumor growth curves (i, red arrow, time of drug injection), mean mouse body weight (j) and survival Kaplan–Meier plot (k). Data are presented as mean ± s.d. within a–g, i and j. One-way analysis of variance (ANOVA) with Tukey’s multiple comparisons test were used to calculate the exact P values, log-rank Mantel–Cox test was utilized to compare the survival plot in the statistical analyses.
