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    Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair

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    Author
    Wang, Q.
    Zhang, H.
    Xu, H.
    Date
    2018
    Journal
    Theranostics
    Publisher
    Ivyspring International Publisher
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.7150/thno.26717
    Abstract
    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-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.
    Sponsors
    This 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.).
    Keyword
    Combination therapy
    Hybrid hydrogel
    Neuro-regeneration
    Scar-homing liposome
    Spinal cord injury
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85052647777&doi=10.7150%2fthno.26717&partnerID=40&md5=7ba3d3a49023106915ce15fe020dd422; http://hdl.handle.net/10713/9663
    ae974a485f413a2113503eed53cd6c53
    10.7150/thno.26717
    Scopus Count
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    UMB Open Access Articles 2018

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