Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
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
_version_ 1783354753651048448
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
work_keys_str_mv AT wangqingqing novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair
AT zhanghongyu novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair
AT xuhelin novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair
AT zhaoyingzheng novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair
AT lizhengmao novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair
AT lijiawei novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair
AT wanghaoli novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair
AT zhugedeli novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair
AT guoxin novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair
AT xuhuazi novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair
AT jonessalazar novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair
AT lixiaokun novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair
AT jiaxiaofeng novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair
AT xiaojian novelmultidrugdeliveryhydrogelusingscarhomingliposomesimprovesspinalcordinjuryrepair