Cell-Specific, Activatable, and Theranostic Prodrug for Dual-Targeted Cancer Imaging and Therapy

    Authors

    S. Santra; C. Kaittanis; O. J. Santiesteban;J. M. Perez

    Comments

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    Abbreviated Journal Title

    J. Am. Chem. Soc.

    Keywords

    FOLATE RECEPTOR; IN-VIVO; DRUG-DELIVERY; FOLIC-ACID; INFLAMMATORY; DISEASES; BIOLOGICAL EVALUATION; TUMOR-CELLS; NANOPARTICLES; DESIGN; PROBES; Chemistry, Multidisciplinary

    Abstract

    Herein we describe the design and synthesis of a folate doxorubicin conjugate with activatable fluorescence and activatable cytotoxicity. In this study we discovered that the cytotoxicity and fluorescence of doxorubicin are quenched (OFF) when covalently linked with folic acid. Most importantly, when the conjugate is designed with a disulfide bond linking the targeting folate unit and the cytotoxic doxorubicin, a targeted activatable prodrug is obtained that becomes activated (ON) within the cell by glutathione-mediated dissociation and nuclear translocation, showing enhanced fluorescence and cellular toxicity. In our novel design, folic acid acted as both a targeting ligand for the folate receptor as well as a quencher for doxorubicin's fluorescence.

    Journal Title

    Journal of the American Chemical Society

    Volume

    133

    Issue/Number

    41

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    16680

    Last Page

    16688

    WOS Identifier

    WOS:000295997500060

    ISSN

    0002-7863

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