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  • E-64 br For in vivo chemo photothermal

    2020-08-18


    For in vivo chemo-photothermal, photothermal and chemothermal therapy, 70 back tumor-bearing mice were assigned to 7 groups (n = 10) after attaining a tumor volume of 200 mm3. From day 0, the mice were intravenously injected with 150 μL of saline, PMDI (with 60 μg/mL DOX and 50 μg/mL ICG), free DOX and ICG (with 60 μg/mL DOX and 50 μg/mL ICG), PMIs (with 50 μg/mL ICG), free ICG (with 50 μg/mL ICG), PMDs (with 60 μg/mL DOX), and free DOX (with 60 μg/ mL DOX) every day for 10 d. In the laser treatment groups, their tumors were separately irradiated with 808 nm NIR light for 10 min, with power densities of 0.5 W cm−2. The body weight and tumor size were recorded every 2 d. At day 20, the whole lungs were stained with 15% India ink, and lung and liver slices were collected and fixed with for-malin for hematoxylin and eosin (H&E) staining after different treat-ments. The remaining five mice in each group were normally fed for 100 d to assess the survival rate.
    2.15. Studies on MDA-MB-231 orthotopic breast tumor-bearing models
    To establish the orthotopic breast cancer mouse model, 1 × 107 MDA-MB-231-luc breast cancer E-64 were suspended in 100 μL frozen cold PBS and injected into the right side of the fourth fat pad of nude mice as described in a previous report. When the volume of tumors reached approximately 300 mm3, the mice were intravenously injected with 100 μL DINPs and PMDIs (with 60 μg/mL DOX, and 50 μg/mL ICG). The IVIS system was used to acquire in vivo NIRF images at the excitation wavelength of 740 nm at 2, 4, 6 and 12 h after injection. At 12 h after injection, all mice were sacrificed to harvest the tumors and major organs for analysis. Similarly, as described above, an infrared thermal imaging camera was used to record the photothermal cap-ability of 100 μL DINPs and PMDIs (with 60 μg/mL DOX and 50 μg/mL ICG) at power densities of 0.5 W cm−2 for 10 min at 6 h post-injection. For in vivo chemo-photothermal, photothermal and chemothermal  Biomaterials 206 (2019) 1–12
    therapy, when the breast tumor size reached approximately 200 mm3, nude mice were assigned to 8 groups with 10 mice per group and in-jected with 150 μL of saline, PMDIs (with 60 μg/mL DOX and 50 μg/mL ICG), DINPs (with 60 μg/mL DOX and 50 μg/mL ICG), free DOX and ICG (with 60 μg/mL DOX and 50 μg/mL ICG), PMIs (with 50 μg/mL ICG), free ICG (with 50 μg/mL ICG), PMDs (with 60 μg/mL DOX), and free DOX (with 60 μg/mL DOX) every day for 10 d. In the laser treat-ment groups, the tumors were separately irradiated with 808 nm NIR light for 10 min, with power densities of 0.5 W cm−2. Mice were weighed every day, and tumor size was measured every day. On day 20, the whole lungs were stained with 15% India ink and heart, lung, liver, kidney, spleen and tumor slices were collected and fixed with formalin for hematoxylin and eosin (H&E) staining after different treatments. The remaining five mice in each group were normally fed for 80 d to assess the survival rate.
    3. Results and discussion
    3.1. Preparation and characterization of nanoparticles
    Herein, we fabricated biomimetic platelet membrane-cloaking PLGA NPs which allow for co-loading and controlled release of DOX and ICG, thereby providing a platform for combination of che-motherapy and PTT to effectively treat E-64 breast cancer metastasis. The synthesis process was described in Fig. 1. The oil-in-water emulsion solvent evaporation method was used to prepare drug-loading PLGA NPs. Following the sonication and extrusion processes of PLGA NPs and platelet membrane vesicles, platelet membrane-cloaking PLGA NPs, including PMDs, PMIs, PMDIs, were successfully prepared. They dis-played a dark green, light pink and light green color, respectively, de-pending on the loaded cargos (Fig. 2A). The prepared NPs possessed mean diameters of approximately 96.9, 120.6, 122.0 and 122.7 nm for DINPs, PMDs, PMIs, and PMDIs, respectively (Table S1). The particle sizes of NPs were all below 125 nm, indicating that they would de-monstrate good EPR effects and suitability for lymphatic targeting [21,29]. The narrow particle size distribution is shown in Fig. S1, with the polydispersity values below 0.2 for the four NPs.
    The transmission electron microscopy (TEM) images of PM-cloaking PLGA NPs displayed the spherical-shaped and core-shell structures of PMDs, PMIs, and PMDIs (Fig. 2A), suggesting the successful coating of the platelet membrane. The zeta potentials of DINPs, PMDs, PMIs, and PMDIs were −1.5 mV, −22.5 mV, −24.8 mV and −26.6 mV, respec-tively (Table S1). The decrease in surface charge and increase in par-ticle size further reflected the presence of PM on the surface of PLGA NPs. The key membrane proteins in PM, PMIs, PMDs and PMDIs were analyzed by SDS-PAGE western blot analysis. In comparison with PM, Figs. 2B and 3D shows that PM-cloaking PLGA NPs all displayed similar protein compositions, suggesting that the preparation steps did not af-fect the key proteins in PM.