Fig. 5: CD47p/AZE–paclitaxome-2 enhanced tumor delivery and bolstered anti-TNBC efficacy with decreased distribution to MPS.
a, Synthesis of DSPE–CD47p. b, The representative DLS size distribution of various Cy5/paclitaxome-2 by intensity. c,d, DLS size (c) and zeta potential (d) of CD47p/AZE–paclitaxome-2 monitoring over a 15-day period at 4 °C (n = 3 independent experiments per group). e–g, Blood kinetics (e), tissue distribution (f) and PTX release rate in tumors (g) at 24 h in orthotopic 4T1-Luc2 tumor mouse model (n = 3 mice per group, tumors ~300 mm3). Mice received a single i.v. injection for Taxol (20 mg PTX kg−1, MTD), PTX/Lipo–SM (40 mg PTX kg−1, MTD), Abraxane and various paclitaxome-2 (MTD) at 70 mg PTX kg−1. h, Lago optical ex vivo photograph of various organs at 24 h in orthotopic 4T1-Luc2 tumor mouse model (n = 3 mice per group, tumor size ~300 mm3) after an i.v. injection with free DSPE–Cy5 and various DSPE–Cy5 tagged paclitaxome-2. i, Representative images of extravasation and penetration for various paclitaxome-2 within the tumors from h (n = 3 tumors per group). 4,6-diamidino-2-phenylindole (DAPI)-stained nuclei (blue). PECAM1 primary antibody and Alexa Fluor 488 secondary antibody labeled blood vessels (green). Scale bars, 50 μm. j–o, antitumor efficacy in orthotopic 4T1-Luc2 tumor-bearing mice with metastasis (n = 5 mice per group, primary tumors: ~300 mm3). j, On day 16, 26 and 35, mice bioluminescence imaging (BLI) were measured by using Lago spectral imaging. k, BLI of lung in mice ex vivo to show metastasis on day 35. l, mean tumor volume determined by a caliper (red arrow indicates the time of drug injection). m,n, primary tumor weight (m) and quantification of BLI for lung metastasis (n) from l via Lago optical imager. o, Kaplan–Meier survival plot from a separate investigation in which mice (n = 5 mice per group, primary tumors, ~300 mm3) received the same treatments as l. Data are presented as mean ± s.d. (c–g,l–n). One-way ANOVA with Tukey’s multiple comparisons test were used to calculate the exact P values in e,f,l–n, log-rank Mantel–Cox test was utilized to compare the survival plot in o.
