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Cancer-Cell-Specific Induction of Apoptosis Using Mesoporous Silica Nanoparticles as Drug-Delivery Vectors

Authors

  • Jessica M. Rosenholm,

    1. Center for Functional Materials Department of Physical Chemistry Åbo Akademi University Porthansgatan 3–5, 2500 Turku (Finland)
    2. Current address: Nano Biomedical Research Center Med-X Institute Shanghai Jiao Tong University 1954 Huashan Road, Shanghai 200030 (P.R. China)
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  • Emilia Peuhu,

    1. Turku Center for Biotechnology Åbo Akademi University and University of Turku Artillerigatan 6A, 20520 Turku (Finland)
    2. Department of Biology Åbo Akademi University Artillerigatan 6A, 20520 Turku (Finland)
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  • Laurel Tabe Bate-Eya,

    1. Turku Center for Biotechnology Åbo Akademi University and University of Turku Artillerigatan 6A, 20520 Turku (Finland)
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  • John E. Eriksson,

    1. Turku Center for Biotechnology Åbo Akademi University and University of Turku Artillerigatan 6A, 20520 Turku (Finland)
    2. Department of Biology Åbo Akademi University Artillerigatan 6A, 20520 Turku (Finland)
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  • Cecilia Sahlgren,

    Corresponding author
    1. Turku Center for Biotechnology Åbo Akademi University and University of Turku Artillerigatan 6A, 20520 Turku (Finland)
    2. Department of Biology Åbo Akademi University Artillerigatan 6A, 20520 Turku (Finland)
    • Turku Center for Biotechnology Åbo Akademi University and University of Turku Artillerigatan 6A, 20520 Turku (Finland).
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  • Mika Lindén

    Corresponding author
    1. Center for Functional Materials Department of Physical Chemistry Åbo Akademi University Porthansgatan 3–5, 2500 Turku (Finland)
    • Center for Functional Materials Department of Physical Chemistry Åbo Akademi University Porthansgatan 3–5, 2500 Turku (Finland)
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Abstract

Targeted delivery of the chemotherapeutic agent methotrexate (MTX) to cancer cells using poly(ethyleneimine)-functionalized mesoporous silica particles as drug-delivery vectors is reported. Due to its high affinity for folate receptors, the expression of which is elevated in cancer cells, MTX serves as both a targeting ligand and a cytotoxic agent. Enhanced cancer-cell apoptosis (programmed cell death) relative to free MTX is thus observed at particle concentrations where nonspecific MTX-induced apoptosis is not observed in the nontargeted healthy cell line, while corresponding amounts of free drug affect both cell lines equally. The particles remain compartmentalized in endo-/lysosomes during the time of observation (up to 72 h), while the drug is released from the particle only upon cell entry, thereby inducing selective apoptosis in the target cells. As MTX is mainly attached to the particle surface, an additional advantage is that the presented carrier design allows for adsorption (loading) of additional drugs into the pore network for therapies based on a combination of drugs.

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