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  • KPT 185 br In vivo anti http www glpbio com simage

    2020-08-18


    2.9. In vivo anticancer efficiency
    Based on efficient accumulation of nanocomposites in tumor region 
    and the attractive synergistic treatment effect for induce MCF-7/ADR cell death. And then in vivo PTT/PDT/chemo-therapy combination therapy experiments were performed by using BPNs-PDA-PEG-PEITC/ DOX on MCF-7/ADR tumor-bearing mice. About 1 × 106 MCF-7/ADR KPT 185 was subcutaneously injected into the front flank of each mouse to acquire MCF-7/ADR tumor modal. When the tumor volume was ap-proximately 100 mm3, mice were randomly separated into ten groups with five mice each group: injection with PBS (group 1), free DOX (group 2), BPNs-PDA-PEG/DOX (group 3), BPNs-PDA-PEG-PEITC/DOX (group 4), BPNs-PDA-PEG-PEITC + 660 nm (group 5), BPNs-PDA-PEG-PEITC + 808 nm (group 6), BPNs-PDA-PEG-PEITC/DOX + 660 nm (group 7), BPNs-PDA-PEG-PEITC/DOX + 808 nm (group 8), BPNs-PDA-PEG-PEITC + 660 nm + 808 nm (group 9), BPNs-PDA-PEG-PEITC/ DOX + 660 nm + 808 nm (group 10). The BPNs-PDA-PEG-PEITC and DOX dosages were 3 mg/kg and 7 mg/kg. After injected with ther-apeutic agents, 6 h later, some group tumor regions of mice were ex-posed by the NIR laser (808 nm, 1.2 W/cm2) for 5 min. The NIR camera was used to record and monitor the temperature of tumor (Fig. 7a and b). The mice treated with BPNs-PDA-PEG-PEITC and BPNs-PDA-PEG-PEITC/DOX, their tumor surface temperatures had a significant in-crease and were maintained at about 53.5 °C during NIR light exposure
    Fig. 5. (a) Mutant p53 expression detected by western blotting. (b) Cell viability of MCF-7 cells treated with BPNs-PDA-PEG, BPNs-PDA-PEG-PEITC, DOX, BPNs-PDA-PEG/DOX and BPNs-PDA-PEG-PEITC/DOX at different DOX concentrations of and the corre-sponding amount of nanocarriers without loading drug. (c) Growth inhibition of MCF-7/ADR cells treated with BPNs-PDA-PEG, BPNs-PDA-PEG-PEITC, DOX, BPNs-PDA-PEG/DOX, BPNs-PDA-PEG-PEITC/ DOX, BPNs-PDA-PEG-PEITC + 660 nm, BPNs-PDA-PEG-PEITC + 808 nm, BPNs-PDA-PEG-PEITC/DOX +
    different DOX concentrations of and the corre-sponding amount of nanocarriers without loading drug. (d) Schematic illustration of the endocytosis of BPNs-PDA-PEG-PEITC/DOX and the subsequent re-versal of mutant p53-mediated multidrug resistance (*p < 0.05, **p < 0.01, ***p < 0.001).
    Fig. 6. (a) T1 relaxation rates of BPNs-PDA-PEG-PEITC-Mn/DOX dispersions at different Mn2+ concentrations. (b) T1-MRI images of BPNs-PDA-PEG-PEITC-Mn/DOX at different concentrations. (c) T1-weighted MRI images of MCF-7/ADR tumor-bearing mice taken before injection and 1, 6, and 12 h post in-jection of BPNs-PDA-PEG-PEITC-Mn/DOX.
    Fig. 7. (a) The infrared thermal camera images of MCF-7/ADR tumor-bearing mice injected with PBS, BPNs-PDA-PEG-PEITC, and BPNs-PDA-PEG-PEITC/DOX exposed with 808 nm NIR laser (1.2 W/cm2) at 0, 60, 180, and 300 s. (b) Tumor region temperature changes of different groups during NIR laser irradiation. (c) Changes of mice tumor volumes of different treatment groups. (d) Photos of the tumors removed from different treatment groups. (e) H&E staining of tumors collected from different treatment groups (**p < 0.01, ***p < 0.001).
    which were able to induce cancer cell death in a few minutes. However, the tumor region temperature of PBS group had a negligible change during the NIR laser irradiation. After receiving various treatments, the tumor sizes were measured every 2 days by a digital caliper (Fig. 7c). The mice tumor sizes which received free DOX or BPNs-PDA-PEG/DOX present a slight reduction compared with PBS group suggesting that antitumor effect of chemotherapy drug to resistant tumor was limited. After treated with BPNs-PDA-PEG-PEITC/DOX, a moderately better antitumor effect on resistant tumor compared with DOX and BPNs-PDA-PEG/DOX groups could be observed that was due to the presentence of PEITC reversing MDR. In addition, both of PDT alone (BPNs-PDA-PEG-PEITC + 660 nm) and PTT alone (BPNs-PDA-PEG-PEITC + 808 nm) could inhibit partially tumor growth. The dual synergistic treatment groups, BPNs-PDA-PEG-PEITC/DOX + 660 nm, BPNs-PDA-PEG-PEITC/ DOX + 808 nm and BPNs-PDA-PEG-PEITC + 660 nm + 808 nm, fur-ther showed the improved tumor growth inhibition effect and the triple 
    synergistic treatment group, BPNs-PDA-PEG-PEITC/ DOX + 660 nm + 808 nm, showed the best treatment effect. At the end of therapy (14 day), the mice were sacrificed humanely and the tumors were dissected. Fig. 7d showed the photos of the tumors of different treatment groups and the BPNs-PDA-PEG-PEITC/ DOX + 660 nm + 808 nm group presented the smallest tumor volume. Fig. 7e displayed the hematoxylin-eosin (H&E) staining of tumor tissue slices which further demonstrated that cancer cells of PBS group keep their normal morphology and the tumor tissue necrosis area of BPNs-PDA-PEG-PEITC/DOX + 660 nm + 808 nm group was larger than the other treatment groups indicating that the combination of PEITC with nanocarrier could enhance the therapeutic effects of DOX to MDR tumor cells and the application of synergistic PTT/PDT could further increase destruction of resistant tumor cells. Fig. S13 showed the body weight variations of different groups. It could be found that the mice treated with free DOX have a weight loss which indicated the potential