{"title":"通过抑制肿瘤中的 Nrf2/ARE 信号通路实现多模式光动力疗法","authors":"Xin Duan, Bingjian Xue, Zimeng Xu, Zixu Niu","doi":"10.1021/acsbiomaterials.4c01643","DOIUrl":null,"url":null,"abstract":"<p><p>Photodynamic therapy (PDT) has been widely used in the clinical therapy of various tumors, especially superficial tumors. However, the tumor microenvironment presents hypoxia, as well as the inherent antioxidant system (e.g., Nrf2) of tumor cells limits the therapeutic outcomes. Herein, a cascade-responsive \"oxidative stress amplifier\" (named EZ@TD) is designed by encapsulating manganese-doped carbon dots acting as a photosensitizer and catalase (CAT)-like nanozyme within pH-sensitive ZIF-8 and Zn<sup>2+</sup>-activated DNAzyme for relieving hypoxia and efficient Nrf2 gene disruption to enhance PDT. It is demonstrated that EZ@TD synergistically inhibited tumor growth and activated the antitumor immune response by inhibiting the Nrf2/ARE signaling pathway in tumors. We provide a new paradigm for amplifying intracellular oxidative stress by interfering with various signaling pathways.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7018-7029"},"PeriodicalIF":5.4000,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multimodal Photodynamic Therapy by Inhibiting the Nrf2/ARE Signaling Pathway in Tumors.\",\"authors\":\"Xin Duan, Bingjian Xue, Zimeng Xu, Zixu Niu\",\"doi\":\"10.1021/acsbiomaterials.4c01643\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Photodynamic therapy (PDT) has been widely used in the clinical therapy of various tumors, especially superficial tumors. However, the tumor microenvironment presents hypoxia, as well as the inherent antioxidant system (e.g., Nrf2) of tumor cells limits the therapeutic outcomes. Herein, a cascade-responsive \\\"oxidative stress amplifier\\\" (named EZ@TD) is designed by encapsulating manganese-doped carbon dots acting as a photosensitizer and catalase (CAT)-like nanozyme within pH-sensitive ZIF-8 and Zn<sup>2+</sup>-activated DNAzyme for relieving hypoxia and efficient Nrf2 gene disruption to enhance PDT. It is demonstrated that EZ@TD synergistically inhibited tumor growth and activated the antitumor immune response by inhibiting the Nrf2/ARE signaling pathway in tumors. We provide a new paradigm for amplifying intracellular oxidative stress by interfering with various signaling pathways.</p>\",\"PeriodicalId\":8,\"journal\":{\"name\":\"ACS Biomaterials Science & Engineering\",\"volume\":\" \",\"pages\":\"7018-7029\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2024-11-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Biomaterials Science & Engineering\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1021/acsbiomaterials.4c01643\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/17 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Biomaterials Science & Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1021/acsbiomaterials.4c01643","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/17 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
Multimodal Photodynamic Therapy by Inhibiting the Nrf2/ARE Signaling Pathway in Tumors.
Photodynamic therapy (PDT) has been widely used in the clinical therapy of various tumors, especially superficial tumors. However, the tumor microenvironment presents hypoxia, as well as the inherent antioxidant system (e.g., Nrf2) of tumor cells limits the therapeutic outcomes. Herein, a cascade-responsive "oxidative stress amplifier" (named EZ@TD) is designed by encapsulating manganese-doped carbon dots acting as a photosensitizer and catalase (CAT)-like nanozyme within pH-sensitive ZIF-8 and Zn2+-activated DNAzyme for relieving hypoxia and efficient Nrf2 gene disruption to enhance PDT. It is demonstrated that EZ@TD synergistically inhibited tumor growth and activated the antitumor immune response by inhibiting the Nrf2/ARE signaling pathway in tumors. We provide a new paradigm for amplifying intracellular oxidative stress by interfering with various signaling pathways.
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