Dataset Information

Biodegradable Nickel Disulfide Nanozymes with GSH-Depleting Function for High-Efficiency Photothermal-Catalytic Antibacterial Therapy.

ABSTRACT: Bacterial infections caused by pathogens have always been a thorny issue that threatens human health, and there is urgent need to develop a new generation of antimicrobial nano-agents and treatments. Herein, biodegradable nickel disulfide (ND) nanozymes as excellent antibacterial agents that integrate excellent photothermal performance, nano-catalysis property, and glutathione (GSH)-depleting function have been successfully constructed. The ND nanozymes can effectively catalyze the decomposition of H₂O₂ to produce ?OH, and the hyperthermia of ND nanozymes generated by photothermal therapy (PTT) can further increase its catalytic activity, which provides rapid and effective bacterial killing effect compared with nano-catalytic treatment or PTT alone. Surprisingly, the ND nanozymes have the ability of GSH consumption, thus enhancing its sterilization effect. Moreover, the ND nanozymes are biodegradable nanomaterials that do not cause any significant toxicity in vivo. Collectively, the ND nanozymes with excellent photothermal performance, catalytic activity, and GSH-depleting function are used for high-efficiency sterilization.

SUBMITTER: Wang X

PROVIDER: S-EPMC7334425 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Biodegradable Nickel Disulfide Nanozymes with GSH-Depleting Function for High-Efficiency Photothermal-Catalytic Antibacterial Therapy.

Wang Xianwen X Fan Linxin L Cheng Liang L Sun Yanbin Y Wang Xiyu X Zhong Xiaoyan X Shi Qianqian Q Gong Fei F Yang Yu Y Ma Yan Y Miao Zhaohua Z Zha Zhengbao Z

iScience 20200616 7

Bacterial infections caused by pathogens have always been a thorny issue that threatens human health, and there is urgent need to develop a new generation of antimicrobial nano-agents and treatments. Herein, biodegradable nickel disulfide (ND) nanozymes as excellent antibacterial agents that integrate excellent photothermal performance, nano-catalysis property, and glutathione (GSH)-depleting function have been successfully constructed. The ND nanozymes can effectively catalyze the decomposition ...[more]

PMID: 32622263

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Project description:Rhabdomyosarcoma (RMS) cells have recently been reported to be sensitive to oxidative stress. Therefore, we investigated whether concomitant inhibition of the two main antioxidant defense pathways, that is, the thioredoxin (TRX) and the glutathione (GSH) systems, presents a new strategy to trigger cell death in RMS. In this study, we discover that GSH-depleting agents, i.e. γ-glutamylcysteine synthetase inhibitor, buthionine sulfoximine (BSO) or the cystine/glutamate antiporter inhibitor erastin (ERA), synergize with thioredoxin reductase (TrxR) inhibitor auranofin (AUR) to induce cell death in RMS cells. Interestingly, AUR causes accumulation of ubiquitinated proteins when combined with BSO or ERA, in line with recent reports showing that AUR inhibits the proteasome besides TrxR. Consistently, AUR/BSO or AUR/ERA cotreatment increases ubiquitination and expression of the short-lived proteins NOXA and MCL-1, accompanied by increased binding of NOXA to MCL-1. Notably, NOXA knockdown significantly rescues RMS cells from AUR/BSO- or AUR/ERA-induced cell death. In addition, AUR acts together with BSO or ERA to stimulate BAX/BAK and caspase activation. Of note, BSO or ERA abolish the AUR-stimulated increase in GSH levels, leading to reduced GSH levels upon cotreatment. Although AUR/BSO or AUR/ERA cotreatment enhances reactive oxygen species (ROS) production, only thiol-containing antioxidants (i.e., N-acetylcysteine (NAC), GSH), but not the non-thiol-containing ROS scavenger α-Tocopherol consistently suppress AUR/BSO- and AUR/ERA-stimulated cell death in both cell lines. Importantly, re-supply of GSH or its precursor NAC completely prevents AUR/ERA- and AUR/BSO-induced accumulation of ubiquitinated proteins, NOXA upregulation and cell death, indicating that GSH depletion rather than ROS production is critical for AUR/BSO- or AUR/ERA-mediated cell death. Thus, by demonstrating that GSH-depleting agents enhance the antitumor activity of AUR, we highlight new treatment options for RMS by targeting the redox homeostasis.

Dataset Information

Biodegradable Nickel Disulfide Nanozymes with GSH-Depleting Function for High-Efficiency Photothermal-Catalytic Antibacterial Therapy.

Publications

Biodegradable Nickel Disulfide Nanozymes with GSH-Depleting Function for High-Efficiency Photothermal-Catalytic Antibacterial Therapy.

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