Star-Shaped Amphiphilic Hyperbranched Polyglycerol Conjugated with Dendritic Poly(L-lysine) for the Codelivery of Docetaxel and MMP-9 siRNA in Cancer Therapy

X. Zhou, Q. Zheng, C. Wang, Jiake Xu, J.P. Wu, T.B. Kirk, D. Ma, W. Xue

    Research output: Contribution to journalArticle

    51 Citations (Scopus)

    Abstract

    © 2016 American Chemical Society.The drug/gene codelivery is a promising strategy for cancer treatment. Herein, to realize the codelivery of docetaxel and MMP-9 siRNA plasmid efficiently into tumor cells, a star-shaped amphiphilic copolymer consisting of hyperbranched polyglycerol derivative (HPG-C18) and dendritic poly(l-lysine) (PLLD) was synthesized by the click reaction between azido-modified HPG-C18 and propargyl focal point PLLD. The obtained HPG-C18-PLLD could form the nanocomplexes with docetaxel and MMP-9, and the complexes showed good gene delivery ability in vitro by inducing an obvious decrease in MMP-9 protein expression in MCF-7 cells. The apoptosis assay showed that the complex could induce a more significant apoptosis to breast cancer cells than that of docetaxel or MMP-9 used alone. In vivo assay indicated that the codelivery strategy displayed a better effect on tumor inhibition. Moreover, HPG-C18-PLLD displayed lower toxicity as well as better blood compatibility compared to polyethylenimine PEI-25k, which may be the result of that HPG-C18-PLLD showed the comparative MMP-9 delivery ability in vivo compared with PEI-25k even if it showed the slight lower transfection efficiency in vitro. Therefore, HPG-C18-PLLD is a safe and effective carrier for the codelivery of drug/gene, which should be encouraged in tumor therapy.
    Original languageEnglish
    Pages (from-to)12609-12619
    Number of pages11
    JournalACS Applied Materials and Interfaces
    Volume8
    Issue number20
    DOIs
    Publication statusPublished - 2016

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    docetaxel
    Matrix Metalloproteinases
    Small Interfering RNA
    Lysine
    Stars
    Tumors
    Polyetherimides
    Genes
    Cell death
    Assays
    Cells
    Oncology
    Toxicity
    Apoptosis
    Blood
    Polyethyleneimine
    Copolymers
    Drug Carriers
    Derivatives
    Proteins

    Cite this

    @article{b8061aa8da7c4dfea67c07c98633293a,
    title = "Star-Shaped Amphiphilic Hyperbranched Polyglycerol Conjugated with Dendritic Poly(L-lysine) for the Codelivery of Docetaxel and MMP-9 siRNA in Cancer Therapy",
    abstract = "{\circledC} 2016 American Chemical Society.The drug/gene codelivery is a promising strategy for cancer treatment. Herein, to realize the codelivery of docetaxel and MMP-9 siRNA plasmid efficiently into tumor cells, a star-shaped amphiphilic copolymer consisting of hyperbranched polyglycerol derivative (HPG-C18) and dendritic poly(l-lysine) (PLLD) was synthesized by the click reaction between azido-modified HPG-C18 and propargyl focal point PLLD. The obtained HPG-C18-PLLD could form the nanocomplexes with docetaxel and MMP-9, and the complexes showed good gene delivery ability in vitro by inducing an obvious decrease in MMP-9 protein expression in MCF-7 cells. The apoptosis assay showed that the complex could induce a more significant apoptosis to breast cancer cells than that of docetaxel or MMP-9 used alone. In vivo assay indicated that the codelivery strategy displayed a better effect on tumor inhibition. Moreover, HPG-C18-PLLD displayed lower toxicity as well as better blood compatibility compared to polyethylenimine PEI-25k, which may be the result of that HPG-C18-PLLD showed the comparative MMP-9 delivery ability in vivo compared with PEI-25k even if it showed the slight lower transfection efficiency in vitro. Therefore, HPG-C18-PLLD is a safe and effective carrier for the codelivery of drug/gene, which should be encouraged in tumor therapy.",
    author = "X. Zhou and Q. Zheng and C. Wang and Jiake Xu and J.P. Wu and T.B. Kirk and D. Ma and W. Xue",
    year = "2016",
    doi = "10.1021/acsami.6b01611",
    language = "English",
    volume = "8",
    pages = "12609--12619",
    journal = "Applied Materials and Interfaces",
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    publisher = "American Chemical Society",
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    }

    Star-Shaped Amphiphilic Hyperbranched Polyglycerol Conjugated with Dendritic Poly(L-lysine) for the Codelivery of Docetaxel and MMP-9 siRNA in Cancer Therapy. / Zhou, X.; Zheng, Q.; Wang, C.; Xu, Jiake; Wu, J.P.; Kirk, T.B.; Ma, D.; Xue, W.

    In: ACS Applied Materials and Interfaces, Vol. 8, No. 20, 2016, p. 12609-12619.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Star-Shaped Amphiphilic Hyperbranched Polyglycerol Conjugated with Dendritic Poly(L-lysine) for the Codelivery of Docetaxel and MMP-9 siRNA in Cancer Therapy

    AU - Zhou, X.

    AU - Zheng, Q.

    AU - Wang, C.

    AU - Xu, Jiake

    AU - Wu, J.P.

    AU - Kirk, T.B.

    AU - Ma, D.

    AU - Xue, W.

    PY - 2016

    Y1 - 2016

    N2 - © 2016 American Chemical Society.The drug/gene codelivery is a promising strategy for cancer treatment. Herein, to realize the codelivery of docetaxel and MMP-9 siRNA plasmid efficiently into tumor cells, a star-shaped amphiphilic copolymer consisting of hyperbranched polyglycerol derivative (HPG-C18) and dendritic poly(l-lysine) (PLLD) was synthesized by the click reaction between azido-modified HPG-C18 and propargyl focal point PLLD. The obtained HPG-C18-PLLD could form the nanocomplexes with docetaxel and MMP-9, and the complexes showed good gene delivery ability in vitro by inducing an obvious decrease in MMP-9 protein expression in MCF-7 cells. The apoptosis assay showed that the complex could induce a more significant apoptosis to breast cancer cells than that of docetaxel or MMP-9 used alone. In vivo assay indicated that the codelivery strategy displayed a better effect on tumor inhibition. Moreover, HPG-C18-PLLD displayed lower toxicity as well as better blood compatibility compared to polyethylenimine PEI-25k, which may be the result of that HPG-C18-PLLD showed the comparative MMP-9 delivery ability in vivo compared with PEI-25k even if it showed the slight lower transfection efficiency in vitro. Therefore, HPG-C18-PLLD is a safe and effective carrier for the codelivery of drug/gene, which should be encouraged in tumor therapy.

    AB - © 2016 American Chemical Society.The drug/gene codelivery is a promising strategy for cancer treatment. Herein, to realize the codelivery of docetaxel and MMP-9 siRNA plasmid efficiently into tumor cells, a star-shaped amphiphilic copolymer consisting of hyperbranched polyglycerol derivative (HPG-C18) and dendritic poly(l-lysine) (PLLD) was synthesized by the click reaction between azido-modified HPG-C18 and propargyl focal point PLLD. The obtained HPG-C18-PLLD could form the nanocomplexes with docetaxel and MMP-9, and the complexes showed good gene delivery ability in vitro by inducing an obvious decrease in MMP-9 protein expression in MCF-7 cells. The apoptosis assay showed that the complex could induce a more significant apoptosis to breast cancer cells than that of docetaxel or MMP-9 used alone. In vivo assay indicated that the codelivery strategy displayed a better effect on tumor inhibition. Moreover, HPG-C18-PLLD displayed lower toxicity as well as better blood compatibility compared to polyethylenimine PEI-25k, which may be the result of that HPG-C18-PLLD showed the comparative MMP-9 delivery ability in vivo compared with PEI-25k even if it showed the slight lower transfection efficiency in vitro. Therefore, HPG-C18-PLLD is a safe and effective carrier for the codelivery of drug/gene, which should be encouraged in tumor therapy.

    U2 - 10.1021/acsami.6b01611

    DO - 10.1021/acsami.6b01611

    M3 - Article

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    JO - Applied Materials and Interfaces

    JF - Applied Materials and Interfaces

    SN - 1944-8244

    IS - 20

    ER -