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Multifunctional metal-organic framework-based nanoreactor for starvation/oxidation improved indoleamine 2,3-dioxygenase-blockade tumor immunotherapy

Author

Listed:
  • Liangliang Dai

    (Institute of Medical Research, Northwestern Polytechnical University
    Nanyang Technological University)

  • Mengjiao Yao

    (Northwestern Polytechnical University)

  • Zhenxiang Fu

    (Institute of Medical Research, Northwestern Polytechnical University)

  • Xiang Li

    (Northwestern Polytechnical University)

  • Xinmin Zheng

    (Northwestern Polytechnical University)

  • Siyu Meng

    (Institute of Medical Research, Northwestern Polytechnical University)

  • Zhang Yuan

    (Institute of Medical Research, Northwestern Polytechnical University)

  • Kaiyong Cai

    (Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University)

  • Hui Yang

    (Northwestern Polytechnical University)

  • Yanli Zhao

    (Nanyang Technological University)

Abstract

Inhibited immune response and low levels of delivery restrict starvation cancer therapy efficacy. Here, we report on the co-delivery of glucose oxidase (GOx) and indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyltryptophan using a metal-organic framework (MOF)-based nanoreactor, showing an amplified release for tumor starvation/oxidation immunotherapy. The nanosystem significantly overcomes the biobarriers associated with tumor penetration and improves the cargo bioavailability owing to the weakly acidic tumor microenvironment-activated charge reversal and size reduction strategy. The nanosystem rapidly disassembles and releases cargoes in response to the intracellular reactive oxygen species (ROS). GOx competitively consumes glucose and generates ROS, further inducing the self-amplifiable MOF disassembly and drug release. The starvation/oxidation combined IDO-blockade immunotherapy not only strengthens the immune response and stimulates the immune memory through the GOx-activated tumor starvation and recruitment of effector T cells, but also effectively relieves the immune tolerance by IDO blocking, remarkably inhibiting the tumor growth and metastasis in vivo.

Suggested Citation

  • Liangliang Dai & Mengjiao Yao & Zhenxiang Fu & Xiang Li & Xinmin Zheng & Siyu Meng & Zhang Yuan & Kaiyong Cai & Hui Yang & Yanli Zhao, 2022. "Multifunctional metal-organic framework-based nanoreactor for starvation/oxidation improved indoleamine 2,3-dioxygenase-blockade tumor immunotherapy," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30436-y
    DOI: 10.1038/s41467-022-30436-y
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    Cited by:

    1. Liang Zhang & Boxin Zhang & Meng-Jie Zhang & Wenlang Li & Hao Li & Yantian Jiao & Qi-Chao Yang & Shuo Wang & Yuan-Tong Liu & An Song & Hai-Tao Feng & Jianwei Sun & Ryan T. K. Kwok & Jacky W. Y. Lam & , 2025. "Trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapy," Nature Communications, Nature, vol. 16(1), pages 1-16, December.

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