{"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":null,"pages":null},"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\":null,\"pages\":null},\"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.
期刊介绍：
ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics:
Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology
Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions
Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis
Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering
Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends
Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring
Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration
Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials
Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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