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Framework nucleic acid-based confined enzyme cascade for efficient synergistic cancer therapy in vivo

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Abstract

Artificial enzyme cascade systems with confinement effect are highly important in synthetic biology and biomedicine. Herein, a framework nucleic acid-based confined enzyme cascade (FNA-CEC) for synergistic cancer therapy in vivo was developed. The FNA-CEC consisted of glucose oxidase and horseradish peroxidase precisely assembled on an addressable DNA tetrahedron scaffold within few nanometers. Glucose oxidase (GOx) can trigger efficient glucose depletion for tumor starvation therapy, and increase the local concentration of H2O2in situ for enhanced downstream horseradish peroxidase (HRP)-activated prodrug therapy. Due to the spatial-confinement on DNA tetrahedron scaffold, the efficiency of intermediate metabolites transportation between the enzyme cascades was improved. Moreover, FNA-CEC was applied for efficient synergistic cancer therapy in vitro and in vivo. As a simple and efficient approach, the FNA-CEC is expected to expand the toolbox of technologies in synthetic biology and biomedicine.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21705038, 21705043, 21890744, 21705037, 21521063), the National Key R&D Program of China (2019YFA0210100), Natural Science Foundation of Hunan Province (2018JJ3029, 2018JJ3092), China Postdoctoral Science Foundation (2020M672470), and the Open Funding Project of Shandong Key Laboratory of Biochemical Analysis (QUSTHX201808).

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Authors and Affiliations

  1. Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China

    Gezhi Kong, Meng Zhang, Mengyi Xiong, Chan Yang, Yan Zhao, Yue Yang, Zilong Zhao, Guoliang Ke, Xiao-Bing Zhang & Weihong Tan

  2. College of Materials Science and Engineering, Hunan University, Changsha, 410082, China

    Mei Chen

  3. Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, Ministry of Education; Shandong Key Laboratory of Biochemical Analysis; College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China

    Zhi-Ling Song

  4. Hunan Key Laboratory of Biomedical Nanomaterials and Devices, College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou, 412007, China

    Liang Gong

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  1. Gezhi Kong
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  2. Meng Zhang
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  3. Mengyi Xiong
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  4. Mei Chen
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  5. Chan Yang
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  6. Yan Zhao
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  7. Yue Yang
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  10. Liang Gong
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  11. Guoliang Ke
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Correspondence to Guoliang Ke.

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Kong, G., Zhang, M., Xiong, M. et al. Framework nucleic acid-based confined enzyme cascade for efficient synergistic cancer therapy in vivo. Sci. China Chem. 64, 660–665 (2021). https://doi.org/10.1007/s11426-020-9927-9

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  • DOI: https://doi.org/10.1007/s11426-020-9927-9

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