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Enhanced cancer therapy by hypoxia-responsive copper metal-organic frameworks nanosystem.

Authors
  • Zhang, Kai1
  • Meng, Xiangdan2
  • Yang, Zhou3
  • Dong, Haifeng4
  • Zhang, Xueji5
  • 1 State Key Laboratory of Chemical Resource Engineering, Key Laboratory of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China; School of Materials Science and Engineering, University of Science & Technology Beijing, 30 Xueyuan Road, Beijing, 100083, PR China; Beijing Key Laboratory for Bioengineering and Sensing Technology, Research Center for Bioengineering and Sensing Technology, School of Chemistry & Biological Engineering, University of Science & Technology Beijing, 30 Xueyuan Road, Beijing, 100083, PR China. , (China)
  • 2 Beijing Key Laboratory for Bioengineering and Sensing Technology, Research Center for Bioengineering and Sensing Technology, School of Chemistry & Biological Engineering, University of Science & Technology Beijing, 30 Xueyuan Road, Beijing, 100083, PR China. , (China)
  • 3 School of Materials Science and Engineering, University of Science & Technology Beijing, 30 Xueyuan Road, Beijing, 100083, PR China. Electronic address: [email protected] , (China)
  • 4 Beijing Key Laboratory for Bioengineering and Sensing Technology, Research Center for Bioengineering and Sensing Technology, School of Chemistry & Biological Engineering, University of Science & Technology Beijing, 30 Xueyuan Road, Beijing, 100083, PR China. Electronic address: [email protected] , (China)
  • 5 School of Biomedical Engineering, Health Science Centre, Shenzhen University, Shenzhen, PR China. , (China)
Type
Published Article
Journal
Biomaterials
Publication Date
Aug 03, 2020
Volume
258
Pages
120278–120278
Identifiers
DOI: 10.1016/j.biomaterials.2020.120278
PMID: 32781328
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Tumor hypoxia-responsive size-switchable nanosystems for precise delivery of drug into deep tumor show great prospects for killing cancer cells with high specificity and minimal invasiveness. However, the development of versatile nanosystems is still a challenge. Herein, for the first time, we report a novel hypoxia-responsive copper metal-organic framework nanoparticles (Cu-MOF NPs) for chemodynamic therapy and sonodynamic therapy (CDT/SDT). The large size Cu-MOF NPs show good stability under normal oxygen partial pressure and enhance tumor accumulation, and it quickly degraded and released Cu2+ and Ce6 when exposed to the hypoxic tumor microenvironment (TME), significantly reinforced the intratumoral penetration. The internalized Cu2+ reacts with local GSH to deplete GSH and reduce Cu2+ to Cu+, which subsequently reacts with endogenous H2O2 to produce cytotoxic hydroxyl radicals (•OH) through Fenton-like reaction for CDT. The released Ce6 further mediated SDT under US irradiation. The synergistic SDT/CDT efficacy was significantly enhanced owing to the GSH depletion, realizing selective and effective MCF-7 killing with minimal invasiveness. This work presents a novel hypoxia-responsive MOF nanosystem with intrinsic CDT properties, mainly, the MOF nanosystem is flexible to the integration with other therapy approaches. It provides a general strategy to design a hypoxia-responsive MOF nano theranostic platform. Copyright © 2020 Elsevier Ltd. All rights reserved.

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