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Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair
Proper selection and effective delivery of combination drugs targeting multiple pathophysiological pathways key to spinal cord injury (SCI) hold promise to address the thus far scarce clinical therapeutics for improving recovery after SCI. In this study, we aim to develop a clinically feasible way f...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134929/ https://www.ncbi.nlm.nih.gov/pubmed/30214630 http://dx.doi.org/10.7150/thno.26717 |
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author | Wang, Qingqing Zhang, Hongyu Xu, Helin Zhao, Yingzheng Li, Zhengmao Li, Jiawei Wang, Haoli Zhuge, Deli Guo, Xin Xu, Huazi Jones, Salazar Li, Xiaokun Jia, Xiaofeng Xiao, Jian |
author_facet | Wang, Qingqing Zhang, Hongyu Xu, Helin Zhao, Yingzheng Li, Zhengmao Li, Jiawei Wang, Haoli Zhuge, Deli Guo, Xin Xu, Huazi Jones, Salazar Li, Xiaokun Jia, Xiaofeng Xiao, Jian |
author_sort | Wang, Qingqing |
collection | PubMed |
description | Proper selection and effective delivery of combination drugs targeting multiple pathophysiological pathways key to spinal cord injury (SCI) hold promise to address the thus far scarce clinical therapeutics for improving recovery after SCI. In this study, we aim to develop a clinically feasible way for targeted delivery of multiple drugs with different physiochemical properties to the SCI site, detail the underlying mechanism of neural recovery, and detect any synergistic effect related to combination therapy. Methods: Liposomes (LIP) modified with a scar-targeted tetrapeptide (cysteine-alanine-glutamine-lysine, CAQK) were first constructed to simultaneously encapsulate docetaxel (DTX) and brain-derived neurotrophic factor (BDNF) and then were further added into a thermosensitive heparin-modified poloxamer hydrogel (HP) with affinity-bound acidic fibroblast growth factor (aFGF-HP) for local administration into the SCI site (CAQK-LIP-GFs/DTX@HP) in a rat model. In vivo fluorescence imaging was used to examine the specificity of CAQK-LIP-GFs/DTX binding to the injured site. Multiple comprehensive evaluations including biotin dextran amine anterograde tracing and magnetic resonance imaging were used to detect any synergistic effects and the underlying mechanisms of CAQK-LIP-GFs/DTX@HP both in vivo (rat SCI model) and in vitro (primary neuron). Results: The multiple drugs were effectively delivered to the injured site. The combined application of GFs and DTX supported neuro-regeneration by improving neuronal survival and plasticity, rendering a more permissive extracellular matrix environment with improved regeneration potential. In addition, our combination therapy promoted axonal regeneration via moderation of microtubule function and mitochondrial transport along the regenerating axon. Conclusion: This novel multifunctional therapeutic strategy with a scar-homing delivery system may offer promising translational prospects for the clinical treatment of SCI. |
format | Online Article Text |
id | pubmed-6134929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-61349292018-09-13 Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair Wang, Qingqing Zhang, Hongyu Xu, Helin Zhao, Yingzheng Li, Zhengmao Li, Jiawei Wang, Haoli Zhuge, Deli Guo, Xin Xu, Huazi Jones, Salazar Li, Xiaokun Jia, Xiaofeng Xiao, Jian Theranostics Research Paper Proper selection and effective delivery of combination drugs targeting multiple pathophysiological pathways key to spinal cord injury (SCI) hold promise to address the thus far scarce clinical therapeutics for improving recovery after SCI. In this study, we aim to develop a clinically feasible way for targeted delivery of multiple drugs with different physiochemical properties to the SCI site, detail the underlying mechanism of neural recovery, and detect any synergistic effect related to combination therapy. Methods: Liposomes (LIP) modified with a scar-targeted tetrapeptide (cysteine-alanine-glutamine-lysine, CAQK) were first constructed to simultaneously encapsulate docetaxel (DTX) and brain-derived neurotrophic factor (BDNF) and then were further added into a thermosensitive heparin-modified poloxamer hydrogel (HP) with affinity-bound acidic fibroblast growth factor (aFGF-HP) for local administration into the SCI site (CAQK-LIP-GFs/DTX@HP) in a rat model. In vivo fluorescence imaging was used to examine the specificity of CAQK-LIP-GFs/DTX binding to the injured site. Multiple comprehensive evaluations including biotin dextran amine anterograde tracing and magnetic resonance imaging were used to detect any synergistic effects and the underlying mechanisms of CAQK-LIP-GFs/DTX@HP both in vivo (rat SCI model) and in vitro (primary neuron). Results: The multiple drugs were effectively delivered to the injured site. The combined application of GFs and DTX supported neuro-regeneration by improving neuronal survival and plasticity, rendering a more permissive extracellular matrix environment with improved regeneration potential. In addition, our combination therapy promoted axonal regeneration via moderation of microtubule function and mitochondrial transport along the regenerating axon. Conclusion: This novel multifunctional therapeutic strategy with a scar-homing delivery system may offer promising translational prospects for the clinical treatment of SCI. Ivyspring International Publisher 2018-08-07 /pmc/articles/PMC6134929/ /pubmed/30214630 http://dx.doi.org/10.7150/thno.26717 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Wang, Qingqing Zhang, Hongyu Xu, Helin Zhao, Yingzheng Li, Zhengmao Li, Jiawei Wang, Haoli Zhuge, Deli Guo, Xin Xu, Huazi Jones, Salazar Li, Xiaokun Jia, Xiaofeng Xiao, Jian Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair |
title | Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair |
title_full | Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair |
title_fullStr | Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair |
title_full_unstemmed | Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair |
title_short | Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair |
title_sort | novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134929/ https://www.ncbi.nlm.nih.gov/pubmed/30214630 http://dx.doi.org/10.7150/thno.26717 |
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