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Self-assembled aldehyde dehydrogenase-activatable nano-prodrug for cancer stem cell-enriched tumor detection and treatment

Author

Listed:
  • Bowen Li

    (4 Engineering Drive 4)

  • Jianwu Tian

    (4 Engineering Drive 4)

  • Fu Zhang

    (Zhejiang University)

  • Chongzhi Wu

    (Zhejiang University)

  • Zhiyao Li

    (Zhejiang University)

  • Dandan Wang

    (4 Engineering Drive 4)

  • Jiahao Zhuang

    (4 Engineering Drive 4)

  • Siqin Chen

    (4 Engineering Drive 4)

  • Wentao Song

    (4 Engineering Drive 4)

  • Yufu Tang

    (4 Engineering Drive 4)

  • Yuan Ping

    (Zhejiang University)

  • Bin Liu

    (4 Engineering Drive 4)

Abstract

Cancer stem cells, characterized by high tumorigenicity and drug-resistance, are often responsible for tumor progression and metastasis. Aldehyde dehydrogenases, often overexpressed in cancer stem cells enriched tumors, present a potential target for specific anti-cancer stem cells treatment. In this study, we report a self-assembled nano-prodrug composed of aldehyde dehydrogenases activatable photosensitizer and disulfide-linked all-trans retinoic acid for diagnosis and targeted treatment of cancer stem cells enriched tumors. The disulfide-linked all-trans retinoic acid can load with photosensitizer and self-assemble into a stable nano-prodrug, which can be disassembled into all-trans retinoic acid and photosensitizer in cancer stem cells by high level of glutathione. As for the released photosensitizer, overexpressed aldehyde dehydrogenase catalyzes the oxidation of aldehydes to carboxyl under cancer stem cells enriched microenvironment, activating the generation of reactive oxygen species and fluorescence emission. This generation of reactive oxygen species leads to direct killing of cancer stem cells and is accompanied by a noticeable fluorescence enhancement for real-time monitoring of the cancer stem cells enriched microenvironment. Moreover, the released all-trans retinoic acid, as a differentiation agent, reduce the cancer stem cells stemness and improve the cancer stem cells enriched microenvironment, offering a synergistic effect for enhanced anti-cancer stem cells treatment of photosensitizer in inhibition of in vivo tumor growth and metastasis.

Suggested Citation

  • Bowen Li & Jianwu Tian & Fu Zhang & Chongzhi Wu & Zhiyao Li & Dandan Wang & Jiahao Zhuang & Siqin Chen & Wentao Song & Yufu Tang & Yuan Ping & Bin Liu, 2024. "Self-assembled aldehyde dehydrogenase-activatable nano-prodrug for cancer stem cell-enriched tumor detection and treatment," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53771-8
    DOI: 10.1038/s41467-024-53771-8
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    References listed on IDEAS

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