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    Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance

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    Author
    Wang, H.
    Liang, Y.
    Yin, Y.
    Zhang, J.
    Su, W.
    White, A.M.
    Jiang, B.
    Xu, J.
    Zhang, Y.
    Stewart, S.
    Lu, X.
    He, X.
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    Date
    2021-01-12
    Journal
    Nature Communications
    Publisher
    Nature Research
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1038/s41467-020-20588-0
    Abstract
    The transmembrane P-glycoprotein (P-gp) pumps that efflux drugs are a major mechanism of cancer drug resistance. They are also important in protecting normal tissue cells from poisonous xenobiotics and endogenous metabolites. Here, we report a fucoidan-decorated silica-carbon nano-onion (FSCNO) hybrid nanoparticle that targets tumor vasculature to specifically release P-gp inhibitor and anticancer drug into tumor cells. The tumor vasculature targeting capability of the nanoparticle is demonstrated using multiple models. Moreover, we reveal the superior light absorption property of nano-onion in the near infrared region (NIR), which enables triggered drug release from the nanoparticle at a low NIR power. The released inhibitor selectively binds to P-gp pumps and disables their function, which improves the bioavailability of anticancer drug inside the cells. Furthermore, free P-gp inhibitor significantly increases the systemic toxicity of a chemotherapy drug, which can be resolved by delivering them with FSCNO nanoparticles in combination with a short low-power NIR laser irradiation. Copyright 2021, The Author(s).
    Sponsors
    This work was supported by grants from the National Institutes of Health (NIH R01CA206366 and R01CA243023).
    Keyword
    drug efflux pumps
    multi-drug resistant cancer cells
    P-glycoprotein inhibition
    tumor vasculature targeted nanovesicle
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/15179
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-020-20588-0
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