11 July 2007 Activatable quantum dots for mouse non-invasive fluorescence imaging
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Abstract
Non-invasive near infrared fluorescence imaging of mice models is a very attractive tool for fastening the development of new therapeutics. Two classes of labels exist for the near infrared domain: organic dyes and quantum dots (QDs). QDs are inorganic luminescent semi-conductor nano-crystals which display very attractive optical features. They are now commercially available for in vivo mouse tests, and new compositions with less toxic elements are currently being developed. The concept of activatable probes, which fluorescence is activated specifically upon the biological process to be visualized, has also been demonstrated to improve the fluorescence image contrast. The construction of activatable probes based on quantum dot labels has therefore been undertaken. Commercial PEGylated quantum dots bearing around 80-100 amino pending groups are used. Long PEG chains are demonstrated to be essential in order to increase the blood circulation time of the particles and avoid their massive storage into the liver. The amino groups coating the QD surface can be used for their further functionalization by either a tumor-targeting ligand, a cleavable spacer bearing a fluorescence inhibitor I, or both. Functionalization of 80% of the amino groups by the inhibitors I leads to more than 99% fluorescence quenching. Cleavable spacers X-L-S-S-L'-I in which S-S is a disulfide bond cleavable by cell internalization, and X a chemical group for QD grafting have been synthesized. The functionalization of the QD by 12 cleavable spacers leads to more than 85% fluorescence inhibition, which can be recovered upon cleavage of the disulfide bonds.
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Jessica Marchand, Jessica Marchand, Anabela Da Silva, Anabela Da Silva, Véronique Josserand, Véronique Josserand, Isabelle Texier, Isabelle Texier, } "Activatable quantum dots for mouse non-invasive fluorescence imaging", Proc. SPIE 6626, Molecular Imaging, 66260E (11 July 2007); doi: 10.1117/12.727831; https://doi.org/10.1117/12.727831
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