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      SERS monitoring of photoinduced-enhanced oxidative stress amplifier on Au@carbon dots for tumor catalytic therapy

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          Abstract

          Currently, artificial enzymes-based photodynamic therapy (PDT) is attractive due to its efficient capacity to change the immunosuppressive tumor microenvironment (TME). It is of great significance to study the therapeutic mechanism of novel artificial enzymes in TME through a monitoring strategy and improve the therapeutic effect. In this study, Au@carbon dots (Au@CDs) nanohybrids with a core-shell structure are synthesized, which not only exhibit tunable enzyme-mimicking activity under near-infrared (NIR) light, but also excellent surface-enhanced Raman scattering (SERS) properties. Therefore, Au@CDs show a good capability for monitoring NIR-photoinduced peroxidase-like catalytic processes via a SERS strategy in tumor. Moreover, the Au@CDs deplete glutathione with the cascade catalyzed reactions, thus elevating intratumor oxidative stress amplifying the reactive oxygen species damage based on the NIR-photoinduced enhanced peroxidase and glutathione oxidase-like activities, showing excellent and fast PDT therapeutic effect promoted by photothermal property in 3 min, finally leading to apoptosis in cancer cells. Through SERS monitoring, it is further found that after removing the NIR light source for 33 min, the reactive oxygen species (ROS) activity of the TME is counteracted and eliminated due to the presence of glutathione. This work presents a guidance to rationally design of artificial enzyme for ROS-involved therapeutic strategies and a new spectroscopic tool to evaluate the tumor catalytic therapy.

          Abstract

          Core-shell structured Au@carbon dots are fabricated to present a photoinduced-enhanced oxidative stress amplification, which can be efficiently used for tumor catalytic therapy by surface-enhanced Raman scattering technique.

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          Free radicals and antioxidants in normal physiological functions and human disease.

          Reactive oxygen species (ROS) and reactive nitrogen species (RNS, e.g. nitric oxide, NO(*)) are well recognised for playing a dual role as both deleterious and beneficial species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. Overproduction of ROS (arising either from mitochondrial electron-transport chain or excessive stimulation of NAD(P)H) results in oxidative stress, a deleterious process that can be an important mediator of damage to cell structures, including lipids and membranes, proteins, and DNA. In contrast, beneficial effects of ROS/RNS (e.g. superoxide radical and nitric oxide) occur at low/moderate concentrations and involve physiological roles in cellular responses to noxia, as for example in defence against infectious agents, in the function of a number of cellular signalling pathways, and the induction of a mitogenic response. Ironically, various ROS-mediated actions in fact protect cells against ROS-induced oxidative stress and re-establish or maintain "redox balance" termed also "redox homeostasis". The "two-faced" character of ROS is clearly substantiated. For example, a growing body of evidence shows that ROS within cells act as secondary messengers in intracellular signalling cascades which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. This review will describe the: (i) chemistry and biochemistry of ROS/RNS and sources of free radical generation; (ii) damage to DNA, to proteins, and to lipids by free radicals; (iii) role of antioxidants (e.g. glutathione) in the maintenance of cellular "redox homeostasis"; (iv) overview of ROS-induced signaling pathways; (v) role of ROS in redox regulation of normal physiological functions, as well as (vi) role of ROS in pathophysiological implications of altered redox regulation (human diseases and ageing). Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing. Topics of current debate are also reviewed such as the question whether excessive formation of free radicals is a primary cause or a downstream consequence of tissue injury.
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            Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?

            Increased generation of reactive oxygen species (ROS) and an altered redox status have long been observed in cancer cells, and recent studies suggest that this biochemical property of cancer cells can be exploited for therapeutic benefits. Cancer cells in advanced stage tumours frequently exhibit multiple genetic alterations and high oxidative stress, suggesting that it might be possible to preferentially eliminate these cells by pharmacological ROS insults. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Abrogation of such drug-resistant mechanisms by redox modulation could have significant therapeutic implications. We argue that modulating the unique redox regulatory mechanisms of cancer cells might be an effective strategy to eliminate these cells.
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              Nanozymes: Classification, Catalytic Mechanisms, Activity Regulation, and Applications

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                Author and article information

                Contributors
                lzhuo@jlu.edu.cn
                zhaob@jlu.edu.cn
                weisong@jlu.edu.cn
                Journal
                Light Sci Appl
                Light Sci Appl
                Light, Science & Applications
                Nature Publishing Group UK (London )
                2095-5545
                2047-7538
                30 September 2022
                30 September 2022
                2022
                : 11
                : 286
                Affiliations
                [1 ]GRID grid.64924.3d, ISNI 0000 0004 1760 5735, State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, , Jilin University, ; Changchun, 130012 China
                [2 ]GRID grid.64924.3d, ISNI 0000 0004 1760 5735, Department of Vascular Surgery of China-Japan Union Hospital, , Jilin University, ; Changchun, 130031 China
                [3 ]GRID grid.64924.3d, ISNI 0000 0004 1760 5735, College of Basic Medical Sciences, , Jilin University, ; Changchun, 130021 China
                [4 ]GRID grid.64924.3d, ISNI 0000 0004 1760 5735, Department of Laboratory Animals, College of Animal Sciences, , Jilin University, ; Changchun, 130062 China
                [5 ]GRID grid.9227.e, ISNI 0000000119573309, State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, , Chinese Academy of Sciences, ; Changchun, 130022 China
                Author information
                http://orcid.org/0000-0003-1939-6423
                http://orcid.org/0000-0001-9814-419X
                Article
                968
                10.1038/s41377-022-00968-5
                9525678
                36180470
                a4da0922-24ea-4a1c-ae22-43219ea471ec
                © The Author(s) 2022

                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
                : 10 March 2022
                : 1 August 2022
                : 23 August 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 22074051
                Award ID: 92161119
                Award ID: 21703230
                Award Recipient :
                Funded by: the Open Funds of the State Key Laboratory of Electroanalytical Chemistry (SKLEAC202006)
                Funded by: Science Technology Research Project of Jilin Provincial Department of Education (JJKH20211040KJ)
                Categories
                Article
                Custom metadata
                © The Author(s) 2022

                raman spectroscopy,plasma-based accelerators
                raman spectroscopy, plasma-based accelerators

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