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Nanodiamond autophagy inhibitor allosterically improves the arsenical-based therapy of solid tumors

Author

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  • Zhifen Cui

    (University of Chinese Academy of Sciences)

  • Yu Zhang

    (University of Chinese Academy of Sciences)

  • Kai Xia

    (University of Chinese Academy of Sciences)

  • Qinglong Yan

    (University of Chinese Academy of Sciences)

  • Huating Kong

    (University of Chinese Academy of Sciences)

  • Jichao Zhang

    (University of Chinese Academy of Sciences)

  • Xiaolei Zuo

    (Shanghai Jiao Tong University)

  • Jiye Shi

    (University of Chinese Academy of Sciences
    University of Oxford)

  • Lihua Wang

    (University of Chinese Academy of Sciences
    East China Normal University)

  • Ying Zhu

    (University of Chinese Academy of Sciences)

  • Chunhai Fan

    (University of Chinese Academy of Sciences
    Shanghai Jiao Tong University)

Abstract

Arsenic trioxide (ATO) is a successful chemotherapeutic drug for blood cancers via selective induction of apoptosis; however its efficacy in solid tumors is limited. Here we repurpose nanodiamonds (NDs) as a safe and potent autophagic inhibitor to allosterically improve the therapeutic efficacy of ATO-based treatment in solid tumors. We find that NDs and ATO are physically separate and functionally target different cellular pathways (autophagy vs. apoptosis); whereas their metabolic coupling in human liver carcinoma cells remarkably enhances programmed cell death. Combination therapy in liver tumor mice model results in ~91% carcinoma decrease as compared with ~28% without NDs. Treated mice show 100% survival rate in 150 days with greatly reduced advanced liver carcinoma-associated symptoms, and ~80% of post-therapy mice survive for over 20 weeks. Our work presents a novel strategy to harness the power of nanoparticles to broaden the scope of ATO-based therapy and more generally to fight solid tumors.

Suggested Citation

  • Zhifen Cui & Yu Zhang & Kai Xia & Qinglong Yan & Huating Kong & Jichao Zhang & Xiaolei Zuo & Jiye Shi & Lihua Wang & Ying Zhu & Chunhai Fan, 2018. "Nanodiamond autophagy inhibitor allosterically improves the arsenical-based therapy of solid tumors," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06749-2
    DOI: 10.1038/s41467-018-06749-2
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