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

Yu-Tong Li; Si-Ting Sheng; Bo Yu; Fan Jia; Kai Wang; Hai-Jie Han; Qiao Jin; You-Xiang Wang; Jian Ji

doi:10.1007/s10118-022-2798-x

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

RESEARCH ARTICLE | Updated：2022-08-19

- An ROS-Responsive Antioxidative Macromolecular Prodrug of Caffeate for Uveitis Treatment
- Chinese Journal of Polymer Science Vol. 40, Issue 9, Pages: 1101-1109(2022)
- Affiliations：
  
  a.MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China
  b.Eye Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
- Author bio：
  
  kaiwang94@zju.edu.cn (K.W.)
  jijian@zju.edu.cn (J.J.)
- Funds：
- DOI：10.1007/s10118-022-2798-x
  CLC：
- Received：15 April 2022，
  
  Revised：2022-05-07，
  
  Accepted：26 May 2022，
  
  Online First：12 July 2022，
  
  Published：01 September 2022
- Accepted：
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Li, Y. T.; Sheng, S. T.; Yu, B.; Jia, F.; Wang, K.; Han, H. J.; Jin, Q.; Wang, Y. X.; Ji, J. An ROS-responsive antioxidative macromolecular prodrug of caffeate for uveitis treatment. Chinese J. Polym. Sci. 2022, 40, 1101–1109

Yu-Tong Li, Si-Ting Sheng, Bo Yu, et al. An ROS-Responsive Antioxidative Macromolecular Prodrug of Caffeate for Uveitis Treatment[J]. Chinese Journal of Polymer Science, 2022, 40(9): 1101-1109.
Li, Y. T.; Sheng, S. T.; Yu, B.; Jia, F.; Wang, K.; Han, H. J.; Jin, Q.; Wang, Y. X.; Ji, J. An ROS-responsive antioxidative macromolecular prodrug of caffeate for uveitis treatment. Chinese J. Polym. Sci. 2022, 40, 1101–1109 DOI： 10.1007/s10118-022-2798-x.

Yu-Tong Li, Si-Ting Sheng, Bo Yu, et al. An ROS-Responsive Antioxidative Macromolecular Prodrug of Caffeate for Uveitis Treatment[J]. Chinese Journal of Polymer Science, 2022, 40(9): 1101-1109. DOI： 10.1007/s10118-022-2798-x.

摘要

We developed an ROS-responsive PEGylated polypeptide-based macromolecular ethyl caffeate (EC) prodrug via phenylboronic esters for the alleviation of uveitis. The antioxidative 4-hydroxy benzyl alcohol (HBA) and EC can be released under the stimulation of ROS

which can effectively protect cells against oxidative stress-induced injury in an ROS-depletion way.

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.

关键词

Keywords

references

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