{"title":"Boosting Tumor Apoptosis and Ferroptosis with Multienzyme Mimetic Au Single-Atom Nanozymes Engaged in Cascade Catalysis","authors":"Ziyi Wang, Runan Chen, Wenying Zhang, Pengchao Sun, Nan Zhang, Yongxing Zhao","doi":"10.1002/adfm.202412767","DOIUrl":null,"url":null,"abstract":"Nanozyme-based catalytic therapy has garnered much attention in cancer treatment for converting endogenous substrates into reactive oxygen species (ROS), which induce oxidative stress damage in tumors. However, the effectiveness of nanozymes is hindered by the limited availability of these endogenous substrates in the tumor microenvironment. To address this, a novel gold-based single-atom nanozyme (AuSAN), glucose oxidase (GOx, G), and lactate oxidase (LOx, L) are meticulously engineered into a highly ordered biomimetic composite nanozyme M/GLB@AuSAN, forming an interconnected cascade catalysis that catalyzes the carbon sources of tumor into ROS as a sustained antitumor strategy. The loaded GOx and LOx aerobically catalyze glucose and lactate to produce H<sub>2</sub>O<sub>2</sub>, which is then rapidly converted into ·OH, O<sub>2</sub><sup>•−</sup>, and O<sub>2</sub> by AuSAN. The generated O<sub>2</sub> serves as a positive feedback substrate for further GOx- and LOx-mediated aerobic catalysis, significantly amplifying cascade catalysis, and thereby enhancing ROS accumulation. The abundant intracellular ROS and scarce carbon sources effectively exacerbate protein phosphorylation, lipid peroxidation, and mitochondrial damage, ultimately provoking tumor apoptosis and ferroptosis in vitro and in vivo. Therefore, the integrated design of GOx/LOx/AuSAN provides a promising strategy to combine multiple enzymatic activities, deplete carbon sources, and enhance ROS production, resulting in the suppression of melanoma progression.","PeriodicalId":112,"journal":{"name":"Advanced Functional Materials","volume":null,"pages":null},"PeriodicalIF":18.5000,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Functional Materials","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1002/adfm.202412767","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Nanozyme-based catalytic therapy has garnered much attention in cancer treatment for converting endogenous substrates into reactive oxygen species (ROS), which induce oxidative stress damage in tumors. However, the effectiveness of nanozymes is hindered by the limited availability of these endogenous substrates in the tumor microenvironment. To address this, a novel gold-based single-atom nanozyme (AuSAN), glucose oxidase (GOx, G), and lactate oxidase (LOx, L) are meticulously engineered into a highly ordered biomimetic composite nanozyme M/GLB@AuSAN, forming an interconnected cascade catalysis that catalyzes the carbon sources of tumor into ROS as a sustained antitumor strategy. The loaded GOx and LOx aerobically catalyze glucose and lactate to produce H2O2, which is then rapidly converted into ·OH, O2•−, and O2 by AuSAN. The generated O2 serves as a positive feedback substrate for further GOx- and LOx-mediated aerobic catalysis, significantly amplifying cascade catalysis, and thereby enhancing ROS accumulation. The abundant intracellular ROS and scarce carbon sources effectively exacerbate protein phosphorylation, lipid peroxidation, and mitochondrial damage, ultimately provoking tumor apoptosis and ferroptosis in vitro and in vivo. Therefore, the integrated design of GOx/LOx/AuSAN provides a promising strategy to combine multiple enzymatic activities, deplete carbon sources, and enhance ROS production, resulting in the suppression of melanoma progression.
期刊介绍:
Firmly established as a top-tier materials science journal, Advanced Functional Materials reports breakthrough research in all aspects of materials science, including nanotechnology, chemistry, physics, and biology every week.
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