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An ROS-Responsive Antioxidative Macromolecular Prodrug of Caffeate for Uveitis Treatment

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Abstract

Uveitis is a sophisticated syndrome showing a high relevance with reactive oxygen species (ROS). Herein, an ROS-responsive PEGylated polypeptide based macromolecular prodrug of herbaceous antioxidant ethyl caffeate (EC) is designed via phenylboronic esters with improved solubility for the alleviation of uveitis. The antioxidative 4-hydroxybenzyl alcohol (HBA) and EC can be released from the macromolecular EC prodrug under the stimulation of ROS, which can effectively protect cells against oxidative stress-induced injury in an ROS-depletion way. The antioxidative and protective effects of the macromolecular EC prodrug in vivo are further verified in a uveitis mouse model. Overall, this work not only provides a handy method to synthesize a phenylboronic ester-bearing EC prodrug which is highly sensitive to pathological ROS, but also depicts a promising future to apply macromolecular antioxidative prodrugs in the treatment of uveitis as well as other ROS-related diseases.

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Acknowledgments

This work was financially supported by National Key Research and Development Project (No. 2020YFE0204400).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China

    Yu-Tong Li, Bo Yu, Fan Jia, Qiao Jin, You-Xiang Wang & Jian Ji

  2. Eye Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China

    Si-Ting Sheng, Kai Wang & Hai-Jie Han

Authors
  1. Yu-Tong Li
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  2. Si-Ting Sheng
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  3. Bo Yu
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  5. Kai Wang
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  7. Qiao Jin
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  8. You-Xiang Wang
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Correspondence to Kai Wang or Jian Ji.

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Li, YT., Sheng, ST., Yu, B. et al. An ROS-Responsive Antioxidative Macromolecular Prodrug of Caffeate for Uveitis Treatment. Chin J Polym Sci 40, 1101–1109 (2022). https://doi.org/10.1007/s10118-022-2798-x

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  • DOI: https://doi.org/10.1007/s10118-022-2798-x

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