Fluorogenic Squaraine Dendrimers for Background-Free Imaging of Integrin Receptors in Cancer Cells |
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Authors: | Dr Pichandi Ashokkumar Dr Mayeul Collot Dr Andrey S Klymchenko |
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Institution: | Laboratoire de Biophotonique et Pharmacologie, CNRS UMR 7213, Faculté de Pharmacie, Université de Strasbourg, 74, Route du Rhin, 67401 Illkirch, France |
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Abstract: | To overcome the limited brightness of existing fluorogenic molecular probes for biomolecular targets, we introduce a concept of fluorogenic dendrimer probe, which undergoes polarity-dependent switching due to intramolecular aggregation-caused quenching of its fluorophores. Based on a rational design of dendrimers with four and eight squaraine dyes, we found that octamer bearing dyes through a sufficiently long PEG(8) linker displays >400-fold fluorescence enhancement from water to non-polar dioxane. High extinction coefficient (≈2,300,000 m −1 cm−1) resulted from eight squaraine dyes and quantum yield (≈25 %) make this octamer the brightest environment-sensitive fluorogenic molecule reported to date. Its conjugate with cyclic RGD used at low concentration (3 nm ) enables integrin-specific fluorescence imaging of cancer cells with high signal-to-background ratio. The developed dendrimer probe is a “golden middle” between molecular probes and nanoparticles, combining small size, turn-on response and high brightness, important for bioimaging. |
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Keywords: | aggregation dendrimers fluorescent probes fluorogenic response integrin receptor |
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