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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...

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Autores principales: Xiao, Zhiyong, Yao, Yingtao, Wang, Zhiyu, Tian, Qing, Wang, Jiedong, Gu, Li, Li, Bo, Zheng, Qixin, Wu, Yongchao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
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.
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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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