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Research Article

Amphiphilic curcumin conjugate-forming nanoparticles as anticancer prodrug and drug carriers: in vitro and in vivo effects

    Huadong Tang*

    Department of Chemical & Petroleum Engineering, University of Wyoming, Laramie, WY 82071, USA

    *Authors contributed equally

    Search for more papers by this author

    ,
    Caitlin J Murphy*

    Department of Animal Science, University of Wyoming, Laramie, WY, 82071, USA

    *Authors contributed equally

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    ,
    Bo Zhang

    Department of Chemical & Petroleum Engineering, University of Wyoming, Laramie, WY 82071, USA

    , ,
    Meihua Sui

    Center for Bionanoengineering & the State Key Laboratory for Chemical Engineering, Department of Chemical & Biological Engineering, Zhejiang University, Hangzhou, 310027, China

    ,
    Edward Alva Van Kirk

    Department of Animal Science, University of Wyoming, Laramie, WY, 82071, USA

    ,
    Xiaowen Feng

    The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310027, China

    &
    William J Murdoch*

    Department of Animal Science, University of Wyoming, Laramie, WY, 82071, USA

    *Authors contributed equally

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    Published Online:https://doi.org/10.2217/nnm.10.67

    Curcumin has been shown to have high cytotoxicity towards various cancer cell lines, but its water insolubility and instability make its bioavailability exceedingly low and, thus, it is generally inactive in in vivo anticancer tests. Here, we report an intracellular-labile amphiphilic surfactant-like curcumin prodrug – curcumin conjugated with two short oligo(ethylene glycol) (Curc-OEG) chains via β-thioester bonds that are labile in the presence of intracellular glutathione and esterase. Curc-OEG formed stable nanoparticles in aqueous conditions and served two roles – as an anticancer prodrug and a drug carrier. As an anticancer prodrug, the formed nanoparticles had a high and fixed curcumin-loading content of 25.3 wt%, and released active curcumin in the intracellular environment. Curc-OEG had high inhibition ability to several cancer cell lines due to apoptosis. Intravenously injected Curc-OEG significantly reduced the tumor weights and tumor numbers in the athymic mice xenografted with intraperitoneal SKOV-3 tumors and subcutaneous (mammary fat pad) MDA-MB-468 tumors. Preliminary systemic toxicity studies found that Curc-OEG did not cause acute and subchronic toxicities to mouse visceral organs at high doses. As drug carriers, Curc-OEG nanoparticles could carry other anticancer drugs, such as doxorubicin and camptothecin, and ship them into drug-resistant cells, greatly enhancing the cytotoxicity of the loaded drug. Thus, Curc-OEG is a promising prototype that merits further study for cancer therapy.

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