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Theranostic cRGD-BioShuttle Constructs Containing Temozolomide- and Cy7 For NIR-Imaging and Therapy

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Author(s): Manfred Wiessler, Ute Hennrich, Rüdiger Pipkorn, Waldemar Waldeck, Liji Cao, Jörg Peter, Volker Ehemann, Wolfhard Semmler, Twan Lammers, Klaus Braun

Journal: Theranostics
ISSN 1838-7640

Volume: 1;
Issue: 1;
Start page: 381;
Date: 2011;
Original page

ABSTRACT
Innovative and personalized therapeutic approaches result from the identification and control of individual aberrantly expressed genes at the transcriptional and post-transcriptional level. Therefore, it is of high interest to establish diagnostic, therapeutic and theranostic strategies at these levels. In the present study, we used the Diels-Alder Reaction with inverse electron demand (DARinv) click chemistry to prepare a series of cyclic RGD-BioShuttle constructs. These constructs carry the near-infrared (NIR) imaging agent Cy7 and the chemotherapeutic agent temozolomide (TMZ). We evaluated their uptake by and their efficacy against integrin αvβ3-expressing MCF7 human breast carcinoma cells. In addition, using a mouse phantom, we analyzed the suitability of this targeted theranostic agent for NIR optical imaging. We observed that the cyclic RGD-based carriers containing TMZ and/or Cy7 were effectively taken up by αvβ3-expressing cells, that they were more effective than free TMZ in inducing cell death, and that they could be quantitatively visualized using NIR fluorescence imaging. Therefore, these targeted theranostic agents are considered to be highly suitable systems for improving disease diagnosis and therapy.
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