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Synergistic enzymatic and bioorthogonal reactions for selective prodrug activation in living systems

Author

Listed:
  • Qingxin Yao

    (National Center for Nanoscience and Technology
    University of Chinese Academy of Sciences)

  • Feng Lin

    (Peking University
    Peking University)

  • Xinyuan Fan

    (Peking University)

  • Yanpu Wang

    (Peking University)

  • Ye Liu

    (National Center for Nanoscience and Technology)

  • Zhaofei Liu

    (Peking University)

  • Xingyu Jiang

    (National Center for Nanoscience and Technology
    University of Chinese Academy of Sciences)

  • Peng R. Chen

    (Peking University
    Peking University)

  • Yuan Gao

    (National Center for Nanoscience and Technology
    University of Chinese Academy of Sciences)

Abstract

Adverse drug reactions (ADRs) restrict the maximum doses applicable in chemotherapy, which leads to failure in cancer treatment. Various approaches, including nano-drug and prodrug strategies aimed at reducing ADRs, have been developed, but these strategies have their own pitfalls. A renovated strategy for ADR reduction is urgently needed. Here, we employ an enzymatic supramolecular self-assembly process to accumulate a bioorthogonal decaging reaction trigger inside targeted cancer cells, enabling spatiotemporally controlled, synergistic prodrug activation. The bioorthogonally activated prodrug exhibits significantly enhanced potency against cancer cells compared with normal cells. This prodrug activation strategy further demonstrates high tumour inhibition efficacy with satisfactory biocompatibility, pharmacokinetics, and safety in vivo. We envision that integration of enzymatic and bioorthogonal reactions will serve as a general small-molecule-based strategy for alleviation of ADRs in chemotherapy.

Suggested Citation

  • Qingxin Yao & Feng Lin & Xinyuan Fan & Yanpu Wang & Ye Liu & Zhaofei Liu & Xingyu Jiang & Peng R. Chen & Yuan Gao, 2018. "Synergistic enzymatic and bioorthogonal reactions for selective prodrug activation in living systems," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07490-6
    DOI: 10.1038/s41467-018-07490-6
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    Cited by:

    1. Yawen You & Qingqing Deng & Yibo Wang & Yanjuan Sang & Guangming Li & Fang Pu & Jinsong Ren & Xiaogang Qu, 2022. "DNA-based platform for efficient and precisely targeted bioorthogonal catalysis in living systems," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Yin Chen & Peng Gao & Lu Huang & Xing Tan & Ningling Zhou & Tong Yang & Hua Qiu & Xin Dai & Sean Michael & Qiufen Tu & Nan Huang & Zhihong Guo & Jianhua Zhou & Zhilu Yang & Hongkai Wu, 2021. "A tough nitric oxide-eluting hydrogel coating suppresses neointimal hyperplasia on vascular stent," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. Qing Wang & Yikang Song & Shuowei Yuan & Yaoji Zhu & Wenjing Wang & Ling Chu, 2024. "Prodrug activation by 4,4’-bipyridine-mediated aromatic nitro reduction," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. Xinyu He & Jie Li & Xinxin Liang & Wuyu Mao & Xinglong Deng & Meng Qin & Hao Su & Haoxing Wu, 2024. "An all-in-one tetrazine reagent for cysteine-selective labeling and bioorthogonal activable prodrug construction," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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