Responsive Contrast Agents: Synthesis and Characterization of a Tunable Series of pH-Sensitive Near-Infrared Pentamethines
Wycisk, Virginia ;  Achazi, Katharina ;  Hillmann, Paul ;  Hirsch, Ole ;  Kuehne, Christian ;  Dernedde, Jens ;  Haag, Rainer ;  Licha, Kai

HaupttitelResponsive Contrast Agents: Synthesis and Characterization of a Tunable Series of pH-Sensitive Near-Infrared Pentamethines
AutorWycisk, Virginia
AutorAchazi, Katharina
AutorHillmann, Paul
AutorHirsch, Ole
AutorKuehne, Christian
AutorDernedde, Jens
AutorHaag, Rainer
AutorLicha, Kai
Seitenzahl10 S.
DDC572 Biochemie
Auch erschienen inACS Omega, 2016, 1 (5), pp 808–817
ZusammenfassungThe demand for responsive dyes in optical imaging is high to achieve a better signal-to-noise ratio and, more specifically, to visualize acidic compartments of the endocytic pathway. Herein, we present a new synthetic route, with a step-by-step synthesis of water-soluble pH-sensitive cyanine dyes exhibiting pKa values in the region of physiological pH, as confirmed by absorption and fluorescence spectra. Moreover, modification of pKa values was achieved by two different substitution patterns, creating tunable pH-sensitive dyes. We demonstrated the functionality of the pH-sensitive dyes and their suitability as contrast agents for cellular uptake studies by preparing dye-labeled cetuximab and transferrin conjugates. Sulfonated head chains increased water solubility and prevented the formation of dimers, even in the context of dye-labeled bioconjugates. Confocal microscopy images of living cells revealed their pH-responsiveness, as specific fluorescence signal enhancements were observed in acidic compartments of the endocytic pathway (endosomes and lysosomes), although the background signal was low in a pH-neutral environment. Using mixtures of conjugates labeled with either a pH-sensitive or non-pH-sensitive dye for the uptake studies, we could follow the receptor binding and distinguish it from the endocytic uptake process of the conjugates in a simultaneous manner. Moreover, we used flow cytometry to quantify the fluorescence and observed a 3-fold signal enhancement for the pH-sensitive dye conjugates over a period of 3 h.
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Fachbereich/EinrichtungFB Biologie, Chemie, Pharmazie
Arbeitsbereich/InstitutInstitut für Chemie und Biochemie
Dokumententyp/-SammlungenWissenschaftlicher Artikel
RechteCopyright des Verlages
Erstellt am08.11.2016 - 13:06:44
Letzte Änderung08.11.2016 - 13:07:53
Statische URLhttp://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000025681