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      Experimental Study of Retention on the Combination of Bifidobacterium with High-Intensity Focused Ultrasound (HIFU) Synergistic Substance in Tumor Tissues

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          Abstract

          High intensity focused ultrasound (HIFU) has been recently regarded to be a new type of technique for non-invasive ablation of local tumors and HIFU synergists could significantly improve its therapeutic efficiency. The therapeutic efficiency of HIFU is greatly limited by the low retention of HIFU synergists in the target area and short residence time. This study aimed to explore a method to increase the deposition of HIFU synergists in tumors. Cationic lipid nanoparticle can be used to enhance the HIFU ablation effect, but there is still a problem for it that the deposition amount in the tumor tissue is small and the residence time is short. Bifidobacterium is highly biosafe and can be selectively colonized in the hypoxic zone of tumor tissue. Cationic lipid nanoparticles can be observed in vitro by attachment to bifidobacterium by electrostatic adsorption. And the effect of the proliferation of bifidobacterium in tumor tissues on the retention amount and retention time of cationic lipid nanoparticles in vivo was evaluated. Results showed that the cationic lipid nanoparticles were linked to the surface of Bifidobacterium effectively in vitro, while in vivo, the retention amount and retention time of cationic lipid nanoparticles could be increased by Bifidobacterium in tumor tissues, which provided a new method for improving the therapeutic efficiency of HIFU.

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          High-intensity focused ultrasound in the treatment of solid tumours.

          Traditionally, surgery has been the only cure for many solid tumours. Technological advances have catalysed a shift from open surgery towards less invasive techniques. Laparoscopic surgery and minimally invasive techniques continue to evolve, but for decades high-intensity focused ultrasound has promised to deliver the ultimate objective - truly non-invasive tumour ablation. Only now, however, with recent improvements in imaging, has this objective finally emerged as a real clinical possibility.
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            Combination bacteriolytic therapy for the treatment of experimental tumors.

            Current chemotherapeutic approaches for cancer are in part limited by the inability of drugs to destroy neoplastic cells within poorly vascularized compartments of tumors. We have here systematically assessed anaerobic bacteria for their capacity to grow expansively within avascular compartments of transplanted tumors. Among 26 different strains tested, one (Clostridium novyi) appeared particularly promising. We created a strain of C. novyi devoid of its lethal toxin (C. novyi-NT) and showed that intravenously injected C. novyi-NT spores germinated within the avascular regions of tumors in mice and destroyed surrounding viable tumor cells. When C. novyi-NT spores were administered together with conventional chemotherapeutic drugs, extensive hemorrhagic necrosis of tumors often developed within 24 h, resulting in significant and prolonged antitumor effects. This strategy, called combination bacteriolytic therapy (COBALT), has the potential to add a new dimension to the treatment of cancer.
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              Bacteria-Mediated Hypoxia-Specific Delivery of Nanoparticles for Tumors Imaging and Therapy.

              The hypoxia region in a solid tumor has been recognized as a complex microenvironment revealing very low oxygen concentration and deficient nutrients. The hypoxic environment reduces the susceptibility of the cancer cells to anticancer drugs, low response of free radicals, and less proliferation of cancer cells in the center of the solid tumors. However, the reduced oxygen surroundings provide an appreciable habitat for anaerobic bacteria to colonize. Here, we present the bacteria-mediated targeting hypoxia to offer the expandable spectra for diagnosis and therapy in cancer diseases. Two delivery approaches involving a cargo-carrying method and an antibody-directed method were designed to deliver upconversion nanorods for imaging and Au nanorods for photothermal ablation upon near-infrared light excitation for two forms of the anaerobic Bifidobacterium breve and Clostridium difficile. The antibody-directed strategy shows the most effective treatment giving stronger imaging and longer retention period and effective therapy to completely remove tumors.
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                Author and article information

                Contributors
                zoujzh@cqmu.edu.cn
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                23 April 2019
                23 April 2019
                2019
                : 9
                : 6423
                Affiliations
                [1 ]ISNI 0000 0000 8653 0555, GRID grid.203458.8, State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, , Chongqing Collaborative Innovation Center for Minimally-invasive and Noninvasive Medicine, College of Biomedical Engineering, Chongqing Medical University, ; Chongqing, 400016 China
                [2 ]Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400021 China
                Article
                42832
                10.1038/s41598-019-42832-4
                6478724
                31015517
                d21fa779-194e-4037-909b-257aaec1f3a7
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 October 2018
                : 9 April 2019
                Funding
                Funded by: Huanan Li, E-mai address:lihuanan1027@163.com Chongqing Medical University No. 1 Yixueyuan Road, Yuzhong District
                Funded by: Qiao Hai1,E-mai address:44325304@qq.com Chongqing Medical University
                Categories
                Article
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                © The Author(s) 2019

                Uncategorized
                targeted therapies,outcomes research
                Uncategorized
                targeted therapies, outcomes research

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