Background Ovarian cancer seriously threatens the lives and health of women, and early diagnosis and treatment are still challenging. Pre-targeting is a promising strategy to improve the treatment efficacy of ovarian cancer and the results of ultrasound imaging. Purpose To explore the effects of a pre-targeting strategy using streptavidin (SA) and paclitaxel (PTX)-loaded phase-shifting poly lactic-co-glycolic acid (PLGA) nanoparticles with perfluoro-n-pentane (PTX-PLGA-SA/PFPs) on the treatment and ultrasound imaging of ovarian cancer. Methods PTX-PLGA/PFPs were prepared with a single emulsion (O/W) solvent evaporation method and SA was attached using carbodiimide. The encapsulation efficiency of PTX and the release characteristics were assessed with high performance liquid chromatography. The phase-change characteristics of the PTX-PLGA-SA/PFPs were investigated. The anti-carcinoembryonic antigen (CEA) antibody (Ab) was covalently attached to PTX-PLGA/PFPs via carbodiimide to create PTX-PLGA-Ab/PFPs. The targeting efficiency of the nanoparticles and the viability of ovarian cancer SKOV3 cells were evaluated in each group using a microscope, flow cytometry, and cell counting kit 8 assays. Results THE PTX-PLGA-SA/PFPs were spheres with a size of 383.0 ± 75.59 nm. The encapsulation efficiency and loading capability of the nanoparticles for PTX were 71.56 ± 6.51% and 6.57 ± 0.61%, respectively. PTX was burst-released up to 70% in 2–3 d. When irradiated at 7.5 W for 3 min, the PTX-PLGA-SA/PFPs visibly enhanced the ultrasonography images (P < 0.05). At temperatures of 45°C and 60°C the nanoparticles phase-shifted into micro-bubbles and the sizes increased. The binding efficiencies of SA and Ab to the PTX-PLGA/PFPs were 97.16 ± 1.20% and 92.74 ± 5.75%, respectively. Pre-targeting resulted in a high binding efficacy and killing effect on SKOV3 cells (P < 0.05). Conclusions The two-step pre-targeting process can significantly enhance the targeting ability of PTX-loaded PLGA nanoparticles for ovarian cancer cells and substantially improve the therapeutic efficacy. This technique provides a new method for ultrasonic imaging and precise chemotherapy for ovarian cancer.
Macrophages are sentinels in the organism which can resist and destroy various bacteria through direct phagocytosis. Here, we reported that expression level of mitochondrial ribosomal protein S35 (Mrps35) continued to decrease over infection time after Listeria monocytogenes (L. monocytogenes) infected macrophages. Our results indicated that knockdown Mrps35 increased the load of L. monocytogenes in macrophages. This result supported that Mrps35 played the crucial roles in L. monocytogenes infection. Moreover, we performed the comprehensive proteomics to analyze the differentially expressed protein of wild type and Mrps35 Knockdown Raw264.7 cells by L. monocytogenes infection over 6 h. Based on the results of mass spectrometry, we presented a wide variety of hypotheses about the mechanism of Mrps35 controlling the L. monocytogenes intracellular proliferation. Among them, experiments confirmed that Mrps35 and 60S ribosomal protein L22‐like 1 (Rpl22l1) were a functional correlation or potentially a compensatory mechanism during L. monocytogenes infection. This study provided new insights into understanding that L. monocytogenes infection changed the basic synthesis or metabolism‐related proteins of host cells.
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