ROS-responsive nanoparticle delivery of ferroptosis inhibitor prodrug to facilitate mesenchymal stem cell-mediated spinal cord injury repair  

作　　者：Renshuai Hua Chenxi Zhao Zhengyu Xu Derong Liu Wenyuan Shen Wenlu Yuan Yan Li Jun Ma Zhishuo Wang Shiqing Feng 

机构地区：[1]Department of Orthopedics,International Science and Technology Cooperation Base of Spinal Cord Injury,Tianjin Key Laboratory of Spine and Spinal Cord Injury,Tianjin Medical University General Hospital,154 Anshan Road,Heping District,Tianjin,300052,China [2]Department of Orthopaedics,Qilu Hospital of Shandong University,Shandong University Centre for Orthopaedics,Advanced Medical Research Institute,Cheeloo College of Medicine,Shandong University,Jinan,Shandong,250012,China [3]Department of Orthopedics,The Second Hospital of Shandong University,Cheeloo College of Medicine,Shandong University,247 Beiyuan Street,Jinan,Shandong,250033,China

出　　处：《Bioactive Materials》2024年第8期438-454,共17页生物活性材料（英文）

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.

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.

关 键 词：Spinal cord injury Huc-MSCs ROS-Responsive nanoparticles Ferroptosis inhibitor 

分 类 号：R651.2[医药卫生—外科学]