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      Persistent luminescence phosphor as in-vivo light source for tumoral cyanobacterial photosynthetic oxygenation and photodynamic therapy.

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          Abstract

          Tumor oxygenation level has been regarded as an attractive target to elevate the efficiency of photodynamic therapy (PDT). Cyanobacterial photosynthesis-mediated reversal of tumor hypoxia could enable an oxygen-boosted PDT, but is limited by scant penetration depth and efficiency of external light. Herein, aiming at the dual purposes of reducing biological toxicity induced by long-term light irradiation and alleviating hypoxia, we here introduce a novel-designed CaAl2O4:Eu,Nd blue persistent luminescence material (PLM) as the in vivo light source after pre-excited in vitro. The ingenious construction of blue-emitting PLM with "optical battery" characteristics activates cyanobacterial cells and verteporfin simultaneously, which performs the successive oxygen supply and singlet oxygen generation without the long-term external excitation, resulting in the modulated tumor hypoxic microenvironment and enhanced photodynamic tumor proliferation inhibition efficiency. Both in vitro cellular assessment and in vivo tumor evaluation results affirm the advantages of self-produced oxygen PDT system and evidence the notable antineoplastic outcome. This work develops an irradiation-free photosynthetic bacteria-based PDT platform for the optimization of both oxygen production capacity and light utilization efficiency in cancer treatment, which is expected to promote the clinical progress of microbial-based photonic therapy.

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          Most cited references38

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          Lactate: a metabolic key player in cancer.

          Increased glucose uptake and accumulation of lactate, even under normoxic conditions (i.e., aerobic glycolysis or the Warburg Effect), is a common feature of cancer cells. This phenomenon clearly indicates that lactate is not a surrogate of tumor hypoxia. Tumor lactate can predict for metastases and overall survival of patients, as shown by several studies of different entities. Metastasis of tumors is promoted by lactate-induced secretion of hyaluronan by tumor-associated fibroblasts that create a milieu favorable for migration. Lactate itself has been found to induce the migration of cells and cell clusters. Furthermore, radioresistance has been positively correlated with lactate concentrations, suggesting an antioxidative capacity of lactate. Findings on interactions of tumor metabolites with immune cells indicate a contribution of lactate to the immune escape. Furthermore, lactate bridges the gap between high lactate levels in wound healing, chronic inflammation, and cancer development. Tumor cells ensure sufficient oxygen and nutrient supply for proliferation through lactate-induced secretion of VEGF, resulting in the formation of new vessels. In summary, accumulation of lactate in solid tumors is a pivotal and early event in the development of malignancies. The determination of lactate should enter further clinical trials to confirm its relevance in cancer biology. ©2011 AACR
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            Innovative Strategies for Hypoxic-Tumor Photodynamic Therapy

            Despite its clinical promise, photodynamic therapy (PDT) suffers from a key drawback associated with its oxygen-dependent nature, which limits its effective use against hypoxic tumors. Moreover, both PDT-mediated oxygen consumption and microvascular damage further increase tumor hypoxia and, thus, impede therapeutic outcomes. In recent years, numerous investigations have focused on strategies for overcoming this drawback of PDT. These efforts, which are summarized in this review, have produced many innovative methods to avoid the limits of PDT associated with hypoxia.
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              Tumor hypoxia causes DNA hypermethylation by reducing TET activity

              Summary Hypermethylation of tumor suppressor gene (TSG) promoters confers growth advantages to cancer cells, but how these changes arise is poorly understood. Here, we report that tumor hypoxia reduces the activity of oxygen-dependent TET enzymes, which catalyze DNA de-methylation through 5-methylcytosine oxidation. This occurs independently of hypoxia-associated alterations in TET expression, proliferation, metabolism, HIF activity or reactive oxygen, but directly depends on oxygen shortage. Hypoxia-induced loss of TET activity increases hypermethylation at gene promoters in vitro. Also in patients, TSG promoters are markedly more methylated in hypoxic tumors, independently of proliferation, stromal cell infiltration and tumor characteristics. Our data suggest cellular selection of hypermethylation events, with almost half of them being ascribable to hypoxia across tumor types. Accordingly, increased hypoxia after vessel pruning in murine breast tumors increases hypermethylation, while restored tumor oxygenation by vessel normalization abrogates this effect. Tumor hypoxia thus acts as a novel regulator underlying DNA methylation.
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                Author and article information

                Journal
                Bioact Mater
                Bioactive materials
                Elsevier BV
                2452-199X
                2452-199X
                Apr 2022
                : 10
                Affiliations
                [1 ] State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, PR China.
                [2 ] Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, PR China.
                [3 ] College of Pharmacy, Qiqihar Medical University, Qiqihar, 161006, PR China.
                [4 ] Department of Ultrasound, Zhongshan Hospital, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, 200032, PR China.
                Article
                S2452-199X(21)00406-0
                10.1016/j.bioactmat.2021.08.030
                8637009
                34901535
                cfe9958d-1a28-4a09-b525-e0d724fe8789
                History

                Photodynamic therapy,Cyanobacteria,Irradiation-free,Oxygenation,Persistent luminescence

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