Local Delivery of Taxol From FGL-Functionalized Self-Assembling Peptide Nanofiber Scaffold Promotes Recovery After Spinal Cord Injury

Frontiers in Cell and Developmental Biology

Bo Li¹  Qing Tian²  Zhiyong Xiao³  Jiedong Wang³  Qixin Zheng³  Yongchao Wu³  Li Gu³  Zhiyu Wang⁴  Yingtao Yao⁵ 

[1] Department of Orthopaedics, Beijing Jishuitan Hospital, Beijing, China;Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China;MoE Key Laboratory for Biomedical Photonics, Collaborative Innovation Center for Biomedical Engineering, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, China;Wuhan National Laboratory for Optoelectronics, Britton Chance Center for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan, China;

关键词: Taxol;    spinal cord injury;    neurite regeneration;    self-assembling peptides;    FGL;    drug release;   

DOI  :  10.3389/fcell.2020.00820

来源: DOAJ

【 摘 要 】

Taxol has been clinically approved as an antitumor drug, and it exerts its antitumor effect through the excessive stabilization of microtubules in cancer cells. Recently, moderate microtubule stabilization by Taxol has been shown to efficiently promote neurite regeneration and functional recovery after spinal cord injury (SCI). However, the potential for the clinical translation of Taxol in treating SCI is limited by its side effects and low ability to cross the blood-spinal cord barrier (BSCB). Self-assembled peptide hydrogels have shown potential as drug carriers for the local delivery of therapeutic agents. We therefore hypothesized that the localized delivery of Taxol by a self-assembled peptide scaffold would promote axonal regeneration by stabilizing microtubules during the treatment of SCI. In the present study, the mechanistic functions of the Taxol-releasing system were clarified in vitro and in vivo using immunofluorescence labeling, histology and neurobehavioral analyses. Based on the findings from the in vitro study, Taxol released from a biological functionalized SAP nanofiber scaffold (FGLmx/Taxol) remained active and promoted neurite extension. In this study, we used a weight-drop contusion model to induce SCI at T9. The local delivery of Taxol from FGLmx/Taxol significantly decreased glial scarring and increased the number of nerve fibers compared with the use of FGLmx and 5% glucose. Furthermore, animals administered FGLmx/Taxol exhibited neurite preservation, smaller cavity dimensions, and decreased inflammation and demyelination. Thus, the local delivery of Taxol from FGLmx/Taxol was effective at promoting recovery after SCI and has potential as a new therapeutic strategy for SCI.

【 授权许可】

Unknown