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      Copper single-atom catalysts with photothermal performance and enhanced nanozyme activity for bacteria‐infected wound therapy

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          Abstract

          Nanozymes have become a new generation of antibiotics with exciting broad-spectrum antibacterial properties and negligible biological toxicity. However, their inherent low catalytic activity limits their antibacterial properties. Herein, Cu single-atom sites/N doped porous carbon (Cu SASs/NPC) is successfully constructed for photothermal-catalytic antibacterial treatment by a pyrolysis-etching-adsorption-pyrolysis (PEAP) strategy. Cu SASs/NPC have stronger peroxidase-like catalytic activity, glutathione (GSH)-depleting function, and photothermal property compared with non-Cu-doped NPC, indicating that Cu doping significantly improves the catalytic performance of nanozymes. Cu SASs/NPC can effectively induce peroxidase-like activity in the presence of H 2O 2, thereby generating a large amount of hydroxyl radicals (•OH), which have a certain killing effect on bacteria and make bacteria more susceptible to temperature. The introduction of near-infrared (NIR) light can generate hyperthermia to fight bacteria, and enhance the peroxidase-like catalytic activity, thereby generating additional •OH to destroy bacteria. Interestingly, Cu SASs/NPC can act as GSH peroxidase (GSH-Px)-like nanozymes, which can deplete GSH in bacteria, thereby significantly improving the sterilization effect. PTT-catalytic synergistic antibacterial strategy produces almost 100% antibacterial efficiency against Escherichia coli ( E. coli) and methicillin-resistant Staphylococcus aureus ( MRSA). In vivo experiments show a better PTT-catalytic synergistic therapeutic performance on MRSA-infected mouse wounds. Overall, our work highlights the wide antibacterial and anti-infective bio-applications of Cu single-atom-containing catalysts.

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          Highlights

          • Uniform Cu SASs/NPC were fabricated by a pyrolysis-etching-adsorption-pyrolysis strategy.

          • Cu SASs/NPC showed excellent photothermal, catalytic, and GSH-depleted properties.

          • Cu SASs/NPC obtained satisfactory PTT-catalytic synergistic antibacterial performance.

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          Most cited references51

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          Targeting microbial biofilms: current and prospective therapeutic strategies.

          Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections. The multifactorial nature of biofilm development and drug tolerance imposes great challenges for the use of conventional antimicrobials and indicates the need for multi-targeted or combinatorial therapies. In this Review, we focus on current therapeutic strategies and those under development that target vital structural and functional traits of microbial biofilms and drug tolerance mechanisms, including the extracellular matrix and dormant cells. We emphasize strategies that are supported by in vivo or ex vivo studies, highlight emerging biofilm-targeting technologies and provide a rationale for multi-targeted therapies aimed at disrupting the complex biofilm microenvironment.
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            Self-Assembled Copper-Amino Acid Nanoparticles for In Situ Glutathione “AND” H2O2 Sequentially Triggered Chemodynamic Therapy

            Nanoformulations that can respond to the specific tumor microenvironment (TME), such as a weakly acidic pH, low oxygen, and high glutathione (GSH), show promise for killing cancer cells with minimal invasiveness and high specificity. In this study, we demonstrate self-assembled copper-amino acid mercaptide nanoparticles (Cu-Cys NPs) for in situ glutathione-activated and H2O2-reinforced chemodynamic therapy for drug-resistant breast cancer. After endocytosis into tumor cells, the Cu-Cys NPs could first react with local GSH, induce GSH depletion, and reduce Cu2+ to Cu+. Subsequently, the generated Cu+ would react with local H2O2 to generate toxic hydroxyl radicals (·OH) via a Fenton-like reaction, which has a fast reaction rate in the weakly acidic TME, that are responsible for tumor-cell apoptosis. Due to the high GSH and H2O2 concentration in tumor cells, which sequentially triggers the redox reactions, Cu-Cys NPs exhibited relatively high cytotoxicity to cancer cells, whereas normal cells were left alive. The in vivo results also proved that Cu-Cys NPs efficiently inhibited drug-resistant breast cancer without causing obvious systemic toxicity. As a novel copper mercaptide nanoformulation responsive to the TME, these Cu-Cys NPs may have great potential in chemodynamic cancer therapy.
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              Synthesis of Copper Peroxide Nanodots for H2O2 Self-Supplying Chemodynamic Therapy

              Chemodynamic therapy (CDT) employs Fenton catalysts to kill cancer cells by converting intracellular H2O2 into hydroxyl radical (•OH), but endogenous H2O2 is insufficient to achieve satisfactory anticancer efficacy. Despite tremendous efforts, engineering CDT agents with specific and efficient H2O2 self-supplying ability remains a great challenge. Here, we report the fabrication of copper peroxide (CP) nanodot, which is the first example of a Fenton-type metal peroxide nanomaterial, and its use as an activatable agent for enhanced CDT by self-supplying H2O2. The CP nanodots were prepared through coordination of H2O2 to Cu2+ with the aid of hydroxide ion, which could be reversed by acid treatment. After endocytosis into tumor cells, acidic environment of endo/lysosomes accelerated the dissociation of CP nanodots, allowing simultaneous release of Fenton catalytic Cu2+ and H2O2 accompanied by a Fenton-type reaction between them. The resulting •OH induced lysosomal membrane permeabilization through lipid peroxidation and thus caused cell death via a lysosome-associated pathway. In addition to pH-dependent •OH generation property, CP nanodots with small particle size showed high tumor accumulation after intravenous administration, which enabled effective tumor growth inhibition with minimal side effects in vivo. Our work not only provides the first paradigm for fabricating Fenton-type metal peroxide nanomaterials, but also presents a new strategy to improve CDT efficacy.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                30 April 2021
                December 2021
                30 April 2021
                : 6
                : 12
                : 4389-4401
                Affiliations
                [a ]Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, 215123, PR China
                [b ]School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, PR China
                [c ]Institute of Clean Energy and Advanced Nanocatalysis, School of Chemistry and Chemical Engineering, Anhui University of Technology, Maanshan, 243002, PR China
                [d ]Beijing Synchrotron Radiation Facility (NSRF), Institute of High Energy Physics, Chinese Academy of Science, Beijing, 100049, China
                [e ]Department of Oncology, Suzhou Xiangcheng People's Hospital, Suzhou, 215131, China
                Author notes
                []Corresponding author. lcheng2@ 123456suda.edu.cn
                [∗∗ ]Corresponding author. zbzha@ 123456hfut.edu.cn
                [∗∗∗ ]Corresponding author. klwuchem@ 123456ahut.edu.cn
                [1]

                These authors contribute equally to this work.

                Article
                S2452-199X(21)00193-6
                10.1016/j.bioactmat.2021.04.024
                8111038
                33997515
                d0c563dc-9823-45e2-814e-308882ec57d1
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 9 March 2021
                : 12 April 2021
                : 14 April 2021
                Categories
                Article

                copper single-atom catalysts,nanozymes,photothermal therapy,antibacterial,catalytic therapy

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