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      A biomimetic nanoreactor for synergistic chemiexcited photodynamic therapy and starvation therapy against tumor metastasis

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      Nature Communications
      Nature Publishing Group UK

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          Abstract

          Photodynamic therapy (PDT) is ineffective against deeply seated metastatic tumors due to poor penetration of the excitation light. Herein, we developed a biomimetic nanoreactor (bio-NR) to achieve synergistic chemiexcited photodynamic-starvation therapy against tumor metastasis. Photosensitizers on the hollow mesoporous silica nanoparticles (HMSNs) are excited by chemical energy in situ of the deep metastatic tumor to generate singlet oxygen ( 1O 2) for PDT, and glucose oxidase (GOx) catalyzes glucose into hydrogen peroxide (H 2O 2). Remarkably, this process not only blocks the nutrient supply for starvation therapy but also provides H 2O 2 to synergistically enhance PDT. Cancer cell membrane coating endows the nanoparticle with biological properties of homologous adhesion and immune escape. Thus, bio-NRs can effectively convert the glucose into 1O 2 in metastatic tumors. The excellent therapeutic effects of bio-NRs in vitro and in vivo indicate their great potential for cancer metastasis therapy.

          Abstract

          Photodynamic therapy is usually ineffective against deeply seated metastatic tumors due to poor penetration of the excitation light. Here, the authors design a biomimetic nanoreactor which can convert nutriment glucose into toxic singlet oxygen via chemiluminescence resonance energy transfer with no light excitation and demonstrate its high efficacy in a mouse lung metastatic model.

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          Most cited references28

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          Tumor metastasis: molecular insights and evolving paradigms.

          Metastases represent the end products of a multistep cell-biological process termed the invasion-metastasis cascade, which involves dissemination of cancer cells to anatomically distant organ sites and their subsequent adaptation to foreign tissue microenvironments. Each of these events is driven by the acquisition of genetic and/or epigenetic alterations within tumor cells and the co-option of nonneoplastic stromal cells, which together endow incipient metastatic cells with traits needed to generate macroscopic metastases. Recent advances provide provocative insights into these cell-biological and molecular changes, which have implications regarding the steps of the invasion-metastasis cascade that appear amenable to therapeutic targeting. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Hypoxia in cancer: significance and impact on clinical outcome.

            Hypoxia, a characteristic feature of locally advanced solid tumors, has emerged as a pivotal factor of the tumor (patho-)physiome since it can promote tumor progression and resistance to therapy. Hypoxia represents a "Janus face" in tumor biology because (a) it is associated with restrained proliferation, differentiation, necrosis or apoptosis, and (b) it can also lead to the development of an aggressive phenotype. Independent of standard prognostic factors, such as tumor stage and nodal status, hypoxia has been suggested as an adverse prognostic factor for patient outcome. Studies of tumor hypoxia involving the direct assessment of the oxygenation status have suggested worse disease-free survival for patients with hypoxic cervical cancers or soft tissue sarcomas. In head & neck cancers the studies suggest that hypoxia is prognostic for survival and local control. Technical limitations of the direct O(2) sensing technique have prompted the use of surrogate markers for tumor hypoxia, such as hypoxia-related endogenous proteins (e.g., HIF-1alpha, GLUT-1, CA IX) or exogenous bioreductive drugs. In many - albeit not in all - studies endogenous markers showed prognostic significance for patient outcome. The prognostic relevance of exogenous markers, however, appears to be limited. Noninvasive assessment of hypoxia using imaging techniques can be achieved with PET or SPECT detection of radiolabeled tracers or with MRI techniques (e.g., BOLD). Clinical experience with these methods regarding patient prognosis is so far only limited. In the clinical studies performed up until now, the lack of standardized treatment protocols, inconsistencies of the endpoints characterizing the oxygenation status and methodological differences (e.g., different immunohistochemical staining procedures) may compromise the power of the prognostic parameter used.
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              Overcoming the Achilles' heel of photodynamic therapy.

              Photodynamic therapy (PDT) has been applied to treat a wide range of medical conditions, including wet age-related macular degeneration psoriasis, atherosclerosis, viral infection and malignant cancers. However, the tissue penetration limitation of excitation light hinders the widespread clinical use of PDT. To overcome this "Achilles' heel", deep PDT, a novel type of phototherapy, has been developed for the efficient treatment of deep-seated diseases. Based on the different excitation sources, including near-infrared (NIR) light, X-ray radiation, and internal self-luminescence, a series of deep PDT techniques have been explored to demonstrate the advantages of deep cancer therapy over conventional PDT excited by ultraviolet-visible (UV-Vis) light. In particular, the featured applications of deep PDT, such as organelle-targeted deep PDT, hypoxic deep PDT and deep PDT-involved multimodal synergistic therapy are discussed. Finally, the future development and potential challenges of deep PDT are also elucidated for clinical translation. It is highly expected that deep PDT will be developed as a versatile, depth/oxygen-independent and minimally invasive strategy for treating a variety of malignant tumours at deep locations.
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                Author and article information

                Contributors
                lina@sdnu.edu.cn
                tangb@sdnu.edu.cn
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                28 November 2018
                28 November 2018
                2018
                : 9
                : 5044
                Affiliations
                GRID grid.410585.d, College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, , Shandong Normal University, ; Jinan, 250014 China
                Article
                7197
                10.1038/s41467-018-07197-8
                6262009
                30487569
                ada2e74b-d64d-4b60-a71b-6c4e26f4d178
                © The Author(s) 2018

                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
                : 27 June 2018
                : 17 October 2018
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