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Drug-Induced Self-Assembly Cascade Nanoreactor for Synergistic Tumor Therapy

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    Biological and Medical Applications of Materials and Interfaces

    Drug-Induced Self-Assembly Cascade Nanoreactor for Synergistic Tumor Therapy
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    • Weicai Wang
      Weicai Wang
      Collaborative Innovation Centre of Tumour Marker Detection Technology, Equipment and Diagnosis-Therapy Integration in Universities of Shandong, Shandong Province Key Laboratory of Detection Technology for Tumour Makers, School of Chemistry and Chemical Engineering, Linyi University, Linyi 276005, China
      Department of Bioscience and Biotechnology, The University of Suwon, Hwaseong City, Gyeonggi-Do 18323, Republic of Korea
      More by Weicai Wang
    • Yuanyuan Wang
      Yuanyuan Wang
      Collaborative Innovation Centre of Tumour Marker Detection Technology, Equipment and Diagnosis-Therapy Integration in Universities of Shandong, Shandong Province Key Laboratory of Detection Technology for Tumour Makers, School of Chemistry and Chemical Engineering, Linyi University, Linyi 276005, China
      More by Yuanyuan Wang
    • Minghui Ma
      Minghui Ma
      Collaborative Innovation Centre of Tumour Marker Detection Technology, Equipment and Diagnosis-Therapy Integration in Universities of Shandong, Shandong Province Key Laboratory of Detection Technology for Tumour Makers, School of Chemistry and Chemical Engineering, Linyi University, Linyi 276005, China
      More by Minghui Ma
    • Hyung Jong Jin*
      Hyung Jong Jin
      Department of Bioscience and Biotechnology, The University of Suwon, Hwaseong City, Gyeonggi-Do 18323, Republic of Korea
      *Email: [email protected]
      More by Hyung Jong Jin
      Orcidhttps://orcid.org/0000-0002-8097-2250
    • Xuemei Li*
      Xuemei Li
      Collaborative Innovation Centre of Tumour Marker Detection Technology, Equipment and Diagnosis-Therapy Integration in Universities of Shandong, Shandong Province Key Laboratory of Detection Technology for Tumour Makers, School of Chemistry and Chemical Engineering, Linyi University, Linyi 276005, China
      *Email: [email protected]
      More by Xuemei Li
      Orcidhttps://orcid.org/0000-0002-8303-8121
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    ACS Applied Materials & Interfaces

    Cite this: ACS Appl. Mater. Interfaces 2022, 14, 39, 44029–44038
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    https://doi.org/10.1021/acsami.2c09947
    Published September 26, 2022
    Copyright © 2022 American Chemical Society
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    Abstract

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    The construction of completely biocompatible and biodegradable tumor suppressors by a simple and reliable method is essential for the clinical application of cancer-targeted drugs. Herein, by inserting glucose oxidase (GOx), catalase (CAT), and chlorin e6 (Ce6) into human serum albumin (HSA) assembly molecules, we constructed a cancer-targeted cascade bioreactor for synergistic starvation and photodynamic therapy (PDT). The modification of HSA could block the GOx activity and reduce the cytotoxicity of normal cells and organs. Through active targeting and passive enhanced permeability and retention effect, the loading of AS1411 could promote the cascade bioreactors to effectively target nucleolin-overexpressed tumors. Once internalized by cancer cells, as a result of catalyzing hydrogen peroxide (H2O2) to produce oxygen (O2), the protein nano-cascade reactor promoted microenvironmental oxygenation, which would subsequently lead to an increase in cytotoxic singlet oxygen (1O2) production under light irradiation as well as the decomposition of intracellular glucose. In vitro and in vivo studies showed that the cascaded nanoreactors could significantly enhance therapeutic efficacy through synergistic starvation therapy and enhanced PDT as well as chemotherapy. This cascade strategy will be demonstrated in clinical applications with huge potential.

    Copyright © 2022 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsami.2c09947.

    • TEM image of hGCP@Ce6@AS1411; fluorescence spectra of HSA-Ce6 with different conjugation ratios; FT-IR spectra and FAM fluorescence spectrum of hGCP@Ce6@AS1411; pH changes induced by the reaction of hGCP@Ce6@AS1411 with different concentrations of glucose; extracellular lactate concentrations after treatment with hGCP@Ce6@AS1411; extracellular and intracellular ROS generation; cell viabilities of L02 cells; representative images of tumor after treatment; and H&E staining of major organs in different groups of mice (PDF)

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    This article is cited by 18 publications.

    1. Weicai Wang, Youcheng Yang, Xiaozu Chen, Tingting Zhao, Xuemei Li. Hollow Mesoporous MnO2 Nanospheres as Light Source-Free Carriers for Synergistic Starvation and Chemiexcited Photodynamic Tumor Therapy. ACS Applied Nano Materials 2023, 6 (16) , 15314-15323. https://doi.org/10.1021/acsanm.3c03336
    2. Yu Xiao, Fuxuan Lai, Mengran Xu, Danning Zheng, Yi Hu, Ming Sun, Na Lv. Dual-Functional Nanoplatform Based on Bimetallic Metal–Organic Frameworks for Synergistic Starvation and Chemodynamic Therapy. ACS Biomaterials Science & Engineering 2023, 9 (4) , 1991-2000. https://doi.org/10.1021/acsbiomaterials.2c01476
    3. Kaiyue Song, Jiang Ming, Bailong Tao, Feng Zhao, Shaorong Huang, Wencheng Wu, Cong Jiang, Xianglong Li. Emerging glucose oxidase-delivering nanomedicines for enhanced tumor therapy. Journal of Controlled Release 2025, 381 , 113580. https://doi.org/10.1016/j.jconrel.2025.02.076
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    15. Ruixuan He, Peida Yang, Aoxue Liu, Yueli Zhang, Yuqi Chen, Cong Chang, Bo Lu. Cascade strategy for glucose oxidase-based synergistic cancer therapy using nanomaterials. Journal of Materials Chemistry B 2023, 11 (41) , 9798-9839. https://doi.org/10.1039/D3TB01325A
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    18. Shaofeng Chen, Rumeng Cao, Ling Xiang, Ziyi Li, Hui Chen, Jiumeng Zhang, Xuli Feng. Research progress in nucleus-targeted tumor therapy. Biomaterials Science 2023, 11 (19) , 6436-6456. https://doi.org/10.1039/D3BM01116J
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    ACS Applied Materials & Interfaces

    Cite this: ACS Appl. Mater. Interfaces 2022, 14, 39, 44029–44038
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsami.2c09947
    Published September 26, 2022
    Copyright © 2022 American Chemical Society
    Request reuse permissions

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