Show simple item record

dc.contributor.authorWang, Q.
dc.contributor.authorZhang, H.
dc.contributor.authorXu, H.
dc.date.accessioned2019-06-21T18:46:24Z
dc.date.available2019-06-21T18:46:24Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85052647777&doi=10.7150%2fthno.26717&partnerID=40&md5=7ba3d3a49023106915ce15fe020dd422
dc.identifier.urihttp://hdl.handle.net/10713/9663
dc.description.abstractProper 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-alanineglutamine- 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. Copyright Ivyspring International Publisher.en_US
dc.description.sponsorshipThis work was supported by the Natural Science Foundation of Zhejiang Province (R18H50001 to J.X.), National Natural Science Foundation of China (81772450 to H.Y.Z., 81722028 and 81572237 to J.X.), Zhejiang Provincial Project of Key Scientific Group (2016C33107 to H.Y.Z.). X. J. was supported partially by R01HL118084 from NIH (to X.J.) and Maryland Stem Cell Research Fund, USA (2018-MSCRFD-4271) (to X.J.).en_US
dc.description.urihttps://dx.doi.org/10.7150/thno.26717en_US
dc.language.isoen-USen_US
dc.publisherIvyspring International Publisheren_US
dc.relation.ispartofTheranostics
dc.subjectCombination therapyen_US
dc.subjectHybrid hydrogelen_US
dc.subjectNeuro-regenerationen_US
dc.subjectScar-homing liposomeen_US
dc.subjectSpinal cord injuryen_US
dc.titleNovel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repairen_US
dc.typeArticleen_US
dc.identifier.doi10.7150/thno.26717


This item appears in the following Collection(s)

Show simple item record