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    Construction of a High-Efficiency Drug and Gene Co-Delivery System for Cancer Therapy from a pH-Sensitive Supramolecular Inclusion between Oligoethylenimine- graft-ß-cyclodextrin and Hyperbranched Polyglycerol Derivative

    Access Status
    Fulltext not available
    Authors
    Zhou, X.
    Xu, L.
    Xu, J.
    Wu, J.
    Kirk, Brett
    Ma, D.
    Xue, W.
    Date
    2018
    Type
    Journal Article
    
    Metadata
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    Citation
    Zhou, X. and Xu, L. and Xu, J. and Wu, J. and Kirk, B. and Ma, D. and Xue, W. 2018. Construction of a High-Efficiency Drug and Gene Co-Delivery System for Cancer Therapy from a pH-Sensitive Supramolecular Inclusion between Oligoethylenimine- graft-ß-cyclodextrin and Hyperbranched Polyglycerol Derivative. ACS Applied Materials and Interfaces. 10 (42): pp. 35812-35829.
    Source Title
    ACS Applied Materials and Interfaces
    DOI
    10.1021/acsami.8b14517
    ISSN
    1944-8244
    Faculty
    Faculty of Science and Engineering
    URI
    http://hdl.handle.net/20.500.11937/71073
    Collection
    • Curtin Research Publications
    Abstract

    © 2018 American Chemical Society. Introducing genes into drug-delivery system for a combined therapy has become a promising strategy for cancer treatment. However, improving the in vivo therapy effect resulted from the high delivery efficiency, low toxicity, and good stability in the blood remains a challenge. For this purpose, the supramolecular inclusion was considered to construct a high-efficiency drug and gene co-delivery system in this work. The oligoethylenimine-conjugated ß-cyclodextrin (ß-CD-PEI600) and benzimidazole-modified four-arm-polycaprolactone-initiated hyperbranched polyglycerol (PCL-HPG-BM) were synthesized as the host and guest molecules, respectively, and then the co-delivery carrier of PCL-HPG-PEI600 was formed from the pH-mediated inclusion interaction between ß-CD and BM. PCL-HPG-PEI600 showed the improved drug (doxorubicin, DOX) and gene (MMP-9 shRNA plasmid, pMMP-9) delivery ability in vivo, and their cellular uptake and intracellular delivery were investigated. Particularly, PCL-HPG-PEI600 showed excellent pMMP-9 delivery ability with significantly higher transfection efficiency than PEI25k due to its excellent serum resistance. For the combined therapy to breast cancer MCF-7 tumor, the co-delivery system of PCL-HPG-PEI600/DOX/pMMP-9 resulted in a much better inhibition effect on MCF-7 cell proliferation and migration in vitro as well as the suppression effect on MCF-7 tumors in vivo compared to those of single DOX or pMMP-9 formulation used. Moreover, PCL-HPG-PEI600 displayed nontoxicity and excellent blood compatibility, suggesting a promising drug and gene co-delivery carrier in combined therapy to tumors.

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