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...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.展开更多
基金financially supported by National Key Research and Development Project (No. 2020YFE0204400)
文摘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.
