摘要
Spinal cord injury(SCI)is a traumatic condition that results in impaired motor and sensory function.Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord,and ferroptosis inhibitors are effective in reducing inflammation and repairing SCI.Although human umbilical cord mesenchymal stem cells(Huc-MSCs)can ameliorate inflammatory microenvironments and promote neural regeneration in SCI,their efficacy is greatly limited by the local microenvironment after SCI.Therefore,in this study,we constructed a drug-release nanoparticle system with synergistic Huc-MSCs and ferroptosis inhibitor,in which we anchored Huc-MSCs by a Tz-A6 peptide based on the CD44-targeting sequence,and combined with the reactive oxygen species(ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at the other end for SCI repair.Meanwhile,we also modified the classic ferroptosis inhibitor Ferrostatin-1(Fer-1)and synthesized a new prodrug Feborastatin-1(Feb-1).The results showed that this treatment regimen significantly inhibited the ferroptosis and inflammatory response after SCI,and promoted the recovery of neurological function in rats with SCI.This study developed a combination therapy for the treatment of SCI and also provides a new strategy for the construction of a drug-coordinated cell therapy system.
基金
supported by the National Key Research and Development Project of Stem Cell and Transformation Research(2019YFA0112100)
Tianjin Key Medical Discipline(Specialty)Construct Project(TJYXZDXK-027A)
International Innovation Summit for Academicians and Experts(22JRRCRC00010).We thank the Large Instrument Sharing Platform of Tianjin Medical University for the availability of the instruments.
作者简介
Renshuai Hua contributed equally to this work.E-mail addresses:renshuai.hua@outlook.com;Chenxi Zhao contributed equally to this work.E-mail addresses:doc_zhao07@163.com;Zhengyu Xu contributed equally to this work.E-mail addresses:dafu_dagui@163.com;Derong Liu.E-mail addresses:xiaoliu19971106@163.com;Wenyuan Shen.E-mail addresses:shenwenyuan66@126.com;Wenlu Yuan.E-mail addresses:lunayuan8029@163.com;Yan Li.E-mail addresses:lala187218@163.com;Jun Ma.E-mail addresses:1651789377@qq.com;Corresponding author:Zhishuo Wang.E-mail addresses:fengshuiling@hotmail.com;Corresponding author:Shiqing Feng.E-mail addresses:sqfeng@tmu.edu.cn。
