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Mitochondria-specific drug release and reactive oxygen species burst induced by polyprodrug nanoreactors can enhance chemotherapy

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  • Wenjia Zhang

    (South China Normal University
    South China Normal University)

  • Xianglong Hu

    (South China Normal University
    South China Normal University)

  • Qi Shen

    (South China Normal University
    South China Normal University)

  • Da Xing

    (South China Normal University
    South China Normal University)

Abstract

Cancer cells exhibit slightly elevated levels of reactive oxygen species (ROS) compared with normal cells, and approximately 90% of intracellular ROS is produced in mitochondria. In situ mitochondrial ROS amplification is a promising strategy to enhance cancer therapy. Here we report cancer cell and mitochondria dual-targeting polyprodrug nanoreactors (DT-PNs) covalently tethered with a high content of repeating camptothecin (CPT) units, which release initial free CPT in the presence of endogenous mitochondrial ROS (mtROS). The in situ released CPT acts as a cellular respiration inhibitor, inducing mtROS upregulation, thus achieving subsequent self-circulation of CPT release and mtROS burst. This mtROS amplification endows long-term high oxidative stress to induce cancer cell apoptosis. This current strategy of endogenously activated mtROS amplification for enhanced chemodynamic therapy overcomes the short lifespan and action range of ROS, avoids the penetration limitation of exogenous light in photodynamic therapy, and is promising for theranostics.

Suggested Citation

  • Wenjia Zhang & Xianglong Hu & Qi Shen & Da Xing, 2019. "Mitochondria-specific drug release and reactive oxygen species burst induced by polyprodrug nanoreactors can enhance chemotherapy," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09566-3
    DOI: 10.1038/s41467-019-09566-3
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    Cited by:

    1. Minglun Liu & Yuncong Chen & Yan Guo & Hao Yuan & Tongxiao Cui & Shankun Yao & Suxing Jin & Huanhuan Fan & Chengjun Wang & Ran Xie & Weijiang He & Zijian Guo, 2022. "Golgi apparatus-targeted aggregation-induced emission luminogens for effective cancer photodynamic therapy," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Yanlin Zhu & Xinxin Wang & Lili Feng & Ruoxi Zhao & Can Yu & Yuanli Liu & Ying Xie & Bin Liu & Yang Zhou & Piaoping Yang, 2024. "Intermetallics triggering pyroptosis and disulfidptosis in cancer cells promote anti-tumor immunity," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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