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Quantum Dot−Aptamer Conjugates for Synchronous Cancer Imaging, Therapy, and Sensing of Drug Delivery Based on Bi-Fluorescence Resonance Energy Transfer

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Laboratory of Nanomedicine and Biomaterials and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, Research Center for Biomolecular Nanotechnology, Department of Life Science, Gwangju Institute of Science and Technology, Buk-gu, Gwangju 500-712, South Korea, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115
Cite this: Nano Lett. 2007, 7, 10, 3065–3070
Publication Date (Web):September 14, 2007
https://doi.org/10.1021/nl071546n
Copyright © 2007 American Chemical Society

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    Abstract

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    We report a novel quantum dot (QD)−aptamer(Apt)−doxorubicin (Dox) conjugate [QD−Apt(Dox)] as a targeted cancer imaging, therapy, and sensing system. By functionalizing the surface of fluorescent QD with the A10 RNA aptamer, which recognizes the extracellular domain of the prostate specific membrane antigen (PSMA), we developed a targeted QD imaging system (QD−Apt) that is capable of differential uptake and imaging of prostate cancer cells that express the PSMA protein. The intercalation of Dox, a widely used antineoplastic anthracycline drug with fluorescent properties, in the double-stranded stem of the A10 aptamer results in a targeted QD−Apt(Dox) conjugate with reversible self-quenching properties based on a Bi-FRET mechanism. A donor−acceptor model fluorescence resonance energy transfer (FRET) between QD and Dox and a donor−quencher model FRET between Dox and aptamer result when Dox intercalated within the A10 aptamer. This simple multifunctional nanoparticle system can deliver Dox to the targeted prostate cancer cells and sense the delivery of Dox by activating the fluorescence of QD, which concurrently images the cancer cells. We demonstrate the specificity and sensitivity of this nanoparticle conjugate as a cancer imaging, therapy and sensing system in vitro.

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     Laboratory of Nanomedicine and Biomaterials and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School.

     Research Center for Biomolecular Nanotechnology, Department of Life Science, Gwangju Institute of Science and Technology.

    §

     Department of Chemical Engineering, Massachusetts Institute of Technology.

    *

     Corresponding authors. E-mail:  [email protected] (S.J.); ofarokhzad@ zeus.bwh.harvard.edu (O.C.F.).

     Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Harvard Medical School.

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