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    Injectable supramolecular hydrogel formed from a-cyclodextrin and PEGylated arginine-functionalized poly(L-lysine) dendron for sustained MMP-9 shRNA plasmid delivery

    Access Status
    Fulltext not available
    Authors
    Lin, Qun
    Yang, Y.
    Hu, Q.
    Guo, Z.
    Liu, T.
    Xu, J.
    Wu, J.
    Kirk, T.
    Ma, D.
    Xue, W.
    Date
    2017
    Type
    Journal Article
    
    Metadata
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    Citation
    Lin, Q. and Yang, Y. and Hu, Q. and Guo, Z. and Liu, T. and Xu, J. and Wu, J. et al. 2017. Injectable supramolecular hydrogel formed from a-cyclodextrin and PEGylated arginine-functionalized poly(L-lysine) dendron for sustained MMP-9 shRNA plasmid delivery. Acta Biomaterialia. 49: pp. 456-471.
    Source Title
    Acta Biomaterialia
    DOI
    10.1016/j.actbio.2016.11.062
    ISSN
    1742-7061
    School
    Department of Mathematics and Statistics
    URI
    http://hdl.handle.net/20.500.11937/52894
    Collection
    • Curtin Research Publications
    Abstract

    © 2016 Acta Materialia Inc.Hydrogels have attracted much attention in cancer therapy and tissue engineering due to their sustained gene delivery ability. To obtain an injectable and high-efficiency gene delivery hydrogel, methoxypolyethylene glycol (MPEG) was used to conjugate with the arginine-functionalized poly(L-lysine) dendron (PLLD-Arg) by click reaction, and then the synthesized MPEG-PLLD-Arg interacted with a-cyclodextrin (a-CD) to form the supramolecular hydrogel by the host-guest interaction. The gelation dynamics, hydrogel strength and shear viscosity could be modulated by a-CD content in the hydrogel. MPEG-PLLD-Arg was confirmed to bind and deliver gene effectively, and its gene transfection efficiency was significantly higher than PEI-25k under its optimized condition. After gelation, MMP-9 shRNA plasmid (pMMP-9) could be encapsulated into the hydrogel matrix in situ and be released from the hydrogels sustainedly, as the release rate was dependent on a-CD content. The released MPEG-PLLD-Arg/pMMP-9 complex still showed better transfection efficiency than PEI-25k and induced sustained tumor cell apoptosis. Also, in vivo assays indicated that this pMMP-9-loaded supramolecular hydrogel could result in the sustained tumor growth inhibition meanwhile showed good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate for long-term gene therapy. Statement of Significance To realize the sustained gene delivery for gene therapy, a supramolecular hydrogel with high-efficiency gene delivery ability was prepared through the host-guest interaction between a-cyclodextrin and PEGylated arginine-functionalized poly(L-lysine) dendron. The obtained hydrogel was injectable and biocompatible with adjustable physicochemical property. More importantly, the hydrogel showed the high-efficiency and sustained gene transfection to our used cells, better than PEI-25k. The supramolecular hydrogel resulted in the sustained tumor growth inhibition meanwhile keep good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate in long-term gene therapy and tissue engineering.

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