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Atom engineering-regulated in situ transition of Cu(I)-Cu(II) for efficiently overcoming cancer drug resistance

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Abstract

The search of highly efficient drugs for overcoming cancer drug resistance continues to be a challenge for scientists. Constructing a metal drug based in situ oxidation-state transition system to disturb the redox balance in cancer cells is a promising approach for overcoming cancer drug resistance. Inspired by natural redox-active copper enzyme centers, we developed a Cu(I)-Cu(II) in situ transition system in this work. Through atom engineering, we fine-tuned the thermodynamic stability of this system to investigate its anticancer activity The results indicated that the synthetic Cu(I)-Cu(II) system could under-go in situ transition in vitro and in vivo, to disrupt the intracellular redox balance and trigger mitochondrial dysfunction and G2/M arrest, leading to apoptosis and overcoming cancer drug resistance This study presents a feasible way to overcome cancer drug resistance by designing an in situ oxidation-state transition metal drug system.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (21877049, 22177038, 32171296), Guangdong Natural Science Foundation (2020B1515120043, 2022A1515012235), the Major Program for Tackling Key Problems of Industrial Technology in Guangzhou (201902020013), Guangdong Pearl River Talent Program (2017GC010354), and the Innovation Team Project in Guangdong Colleges and Universities (2019KCXTD008, 2019KTSCX012).

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, Jinan University, Guangzhou, 510632, China

    Yuequn Zhang, Mingkai Chen, Junping Wang, Fei Cai, Li Ma & Tianfeng Chen

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  1. Yuequn Zhang
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  2. Mingkai Chen
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  3. Junping Wang
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  4. Fei Cai
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  5. Li Ma
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  6. Tianfeng Chen
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Correspondence to Li Ma or Tianfeng Chen.

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Conflict of interest The authors declare no conflict of interest.

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Supporting information The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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11426_2022_1340_MOESM1_ESM.pdf

Atom Engineering-Regulated In Situ Transition of Cu(I)-Cu(II) Entatic State for Efficient Overcoming Cancer Drug Resistance

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Zhang, Y., Chen, M., Wang, J. et al. Atom engineering-regulated in situ transition of Cu(I)-Cu(II) for efficiently overcoming cancer drug resistance. Sci. China Chem. 65, 1879–1884 (2022). https://doi.org/10.1007/s11426-022-1340-6

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