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Cross-linked lipoic acid nanocapsules serve as H2O2 amplifier to strengthen the H2O2-sensitive prodrug activation

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Abstract

The H2O2-triggered prodrug activation represents a hot topic while the low H2O2 level of cancer cells hindered the complete activation of parent drugs and resulted in the poor therapeutic effect. Here, we developed an H2O2 amplifier fabricated by cross-linked lipoic acid nanocapsules (cLANCs), which would selectively elevate the intracellular H2O2 level of cancer cells 3.4-fold higher than that of untreated cancer cells so as to speed up the activation of parent drug from the loaded prodrugs (Pro-5-FU). The cytotoxicity showed that the killing effect of Pro-5-FU loaded in cLANCs (Pro-5-FU@cLANCs) arrived up to 1.6-time higher than that of Pro-5-FU alone against A549 cells, and was even close to free 5-FU. The in vivo anticancer evaluation gave the tumor inhibition rate (TIR) and survival rate (SR) of Pro-5-FU@cLANCs against A549 tumor-bearing nude mice up to 73.1% and 80%, respectively, much higher than those of Pro-5-FU (TIR: 41.2%, SR: 20%) or free 5-FU (TIR: 50.6%, SR: 0%). This nanodrug constructed the first example that utilizes the drug carriers as H2O2 amplifier to strengthen the prodrug activation.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (22201193 and 21975165), the Innovative Research Team Program of Sichuan Province (2021JDTD0015) and the National Natural Science Foundation of Sichuan Province (2023NSFSC1691). We acknowledge the Center of Testing and Analysis, Sichuan University, for the 1H NMR and TEM measurements.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China

    Jiangbing Tan, Xiao Xiao, Yulong Liao, Chunyan Liao & Shiyong Zhang

  2. Department of Pharmacy, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

    Pei Jing

Authors
  1. Jiangbing Tan
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  2. Pei Jing
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  3. Xiao Xiao
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  4. Yulong Liao
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  5. Chunyan Liao
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  6. Shiyong Zhang
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Correspondence to Shiyong Zhang.

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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 https://chem.scichina.com and https://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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Tan, J., Jing, P., Xiao, X. et al. Cross-linked lipoic acid nanocapsules serve as H2O2 amplifier to strengthen the H2O2-sensitive prodrug activation. Sci. China Chem. 66, 2654–2663 (2023). https://doi.org/10.1007/s11426-022-1647-2

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  • DOI: https://doi.org/10.1007/s11426-022-1647-2

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