An activatable multimodal/multifunctional nanoprobe for direct imaging of intracellular drug delivery

    Authors

    R. N. Mitra; M. Doshi; X. L. Zhang; J. C. Tyus; N. Bengtsson; S. Fletcher; B. D. G. Page; J. Turkson; A. J. Gesquiere; P. T. Gunning; G. A. Walter;S. Santra

    Comments

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    Abbreviated Journal Title

    Biomaterials

    Keywords

    Magnetic nanoparticles; Quantum dots; Targeted drug delivery; Bioimaging; Biosensing; RESONANCE ENERGY-TRANSFER; IRON-OXIDE NANOPARTICLES; QUANTUM-DOT; MAGNETIC NANOPARTICLES; CANCER-THERAPY; IN-VITRO; FLUORESCENT; GLUTATHIONE; PROBE; ANGIOGENESIS; Engineering, Biomedical; Materials Science, Biomaterials

    Abstract

    Multifunctional nanoparticles integrated with imaging modalities (such as magnetic resonance and optical) and therapeutic drugs are promising candidates for future cancer diagnostics and therapy. While targeted drug delivery and imaging of tumor cells have been the major focus in engineering nanoparticle probes, no extensive efforts have been made towards developing sensing probes that can confirm and monitor intracellular drug release events. Here, we present quantum dot (Qdot)-iron oxide (IO) based multimodal/multifunctional nanocomposite probe that is optically and magnetically imageable, targetable and capable of reporting on intracellular drug release events. Specifically, the probe consists of a superparamagnetic iron oxide nanoparticle core (IONP) decorated with satellite CdS:Mn/ZnS Qdots where the Qdots themselves are further functionalized with STAT3 inhibitor (an anti-cancer agent), vitamin folate (as targeting motif) and m-polyethylene glycol (mPEG, a hydrophilic dispersing agent). The Qdot luminescence is quenched in this nanocomposite probe ("OFF" state) due to combined electron/energy transfer mediated quenching processes involving IONP, folate and STAT3 agents. Upon intracellular uptake, the probe is exposed to the cytosolic glutathione (GSH) containing environment resulting in restoration of the Qdot luminescence ("ON" state), which reports on uptake and drug release. Probe functionality was validated using fluorescence and MR measurements as well as in vitro studies using cancer cells that overexpress folate receptors. (C) 2011 Elsevier Ltd. All rights reserved.

    Journal Title

    Biomaterials

    Volume

    33

    Issue/Number

    5

    Publication Date

    1-1-2012

    Document Type

    Article

    Language

    English

    First Page

    1500

    Last Page

    1508

    WOS Identifier

    WOS:000300474000028

    ISSN

    0142-9612

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