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Local Delivery of Taxol From FGL-Functionalized Self-Assembling Peptide Nanofiber Scaffold Promotes Recovery After Spinal Cord Injury
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 af...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471253/ https://www.ncbi.nlm.nih.gov/pubmed/32974351 http://dx.doi.org/10.3389/fcell.2020.00820 |
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author | Xiao, Zhiyong Yao, Yingtao Wang, Zhiyu Tian, Qing Wang, Jiedong Gu, Li Li, Bo Zheng, Qixin Wu, Yongchao |
author_facet | Xiao, Zhiyong Yao, Yingtao Wang, Zhiyu Tian, Qing Wang, Jiedong Gu, Li Li, Bo Zheng, Qixin Wu, Yongchao |
author_sort | Xiao, Zhiyong |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7471253 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74712532020-09-23 Local Delivery of Taxol From FGL-Functionalized Self-Assembling Peptide Nanofiber Scaffold Promotes Recovery After Spinal Cord Injury Xiao, Zhiyong Yao, Yingtao Wang, Zhiyu Tian, Qing Wang, Jiedong Gu, Li Li, Bo Zheng, Qixin Wu, Yongchao Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2020-08-21 /pmc/articles/PMC7471253/ /pubmed/32974351 http://dx.doi.org/10.3389/fcell.2020.00820 Text en Copyright © 2020 Xiao, Yao, Wang, Tian, Wang, Gu, Li, Zheng and Wu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Xiao, Zhiyong Yao, Yingtao Wang, Zhiyu Tian, Qing Wang, Jiedong Gu, Li Li, Bo Zheng, Qixin Wu, Yongchao Local Delivery of Taxol From FGL-Functionalized Self-Assembling Peptide Nanofiber Scaffold Promotes Recovery After Spinal Cord Injury |
title | Local Delivery of Taxol From FGL-Functionalized Self-Assembling Peptide Nanofiber Scaffold Promotes Recovery After Spinal Cord Injury |
title_full | Local Delivery of Taxol From FGL-Functionalized Self-Assembling Peptide Nanofiber Scaffold Promotes Recovery After Spinal Cord Injury |
title_fullStr | Local Delivery of Taxol From FGL-Functionalized Self-Assembling Peptide Nanofiber Scaffold Promotes Recovery After Spinal Cord Injury |
title_full_unstemmed | Local Delivery of Taxol From FGL-Functionalized Self-Assembling Peptide Nanofiber Scaffold Promotes Recovery After Spinal Cord Injury |
title_short | Local Delivery of Taxol From FGL-Functionalized Self-Assembling Peptide Nanofiber Scaffold Promotes Recovery After Spinal Cord Injury |
title_sort | local delivery of taxol from fgl-functionalized self-assembling peptide nanofiber scaffold promotes recovery after spinal cord injury |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471253/ https://www.ncbi.nlm.nih.gov/pubmed/32974351 http://dx.doi.org/10.3389/fcell.2020.00820 |
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